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Numéro de publicationUS20070105933 A1
Type de publicationDemande
Numéro de demandeUS 11/636,776
Date de publication10 mai 2007
Date de dépôt11 déc. 2006
Date de priorité11 janv. 2002
Autre référence de publicationCA2473461A1, CA2473461C, CN1630635A, CN100406437C, DE60328161D1, EP1471054A1, EP1471054A4, EP1471054B1, US7199150, US7638551, US8067396, US8101650, US20050043386, US20070142335, US20090326038, US20100035842, WO2003059880A1
Numéro de publication11636776, 636776, US 2007/0105933 A1, US 2007/105933 A1, US 20070105933 A1, US 20070105933A1, US 2007105933 A1, US 2007105933A1, US-A1-20070105933, US-A1-2007105933, US2007/0105933A1, US2007/105933A1, US20070105933 A1, US20070105933A1, US2007105933 A1, US2007105933A1
InventeursTakahide Nishi, Takaichi Shimozato, Futoshi Nara, Shojiro Miyazaki
Cessionnaire d'origineSankyo Company, Limited
Exporter la citationBiBTeX, EndNote, RefMan
Liens externes: USPTO, Cession USPTO, Espacenet
Amino alcohol compounds
US 20070105933 A1
Résumé
A method for the preventing a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a mammal, such as a human, in need thereof, which includes administering to the mammal a pharmaceutically effective amount of a compound of formula (Ia)
wherein R1 and R2 are each hydrogen; R3 is hydrogen; R4 is C1-C2 alkyl; n is 2; X is=N-D, wherein D is hydrogen, C1-C4 alkyl or phenyl; Y is ethylene, ethynylene, —CO—CH2 or phenylene; Z is ethylene or trimethylene; R5 is an unsubstituted C3-C10 cycloalkyl, an unsubstituted C6-C10 aryl, or a C3-C10 cycloalkyl or C6-C10 aryl substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogeno lower alkyl and lower alkoxy; and R6 and R7 are each hydrogen.
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1. A method for the prevention of a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a human in need thereof, which comprises administering to said human a pharmaceutically effective amount of a compound of formula (Ia)
wherein R1 and R2 are each a hydrogen atom;
R3 is a hydrogen atom;
R4 is a C1-C2 alkyl group;
n is 2;
X is=N-D, wherein D is a hydrogen atom, a C1-C4 alkyl group or a phenyl group;
Y is an ethylene group, an ethynylene group, a group of a formula —CO—CH2 or a phenylene group;
Z is an ethylene group or a trimethylene group;
R5is an unsubstituted C3-C10 cycloalkyl group, an unsubstituted C6-C10 aryl group, or a C3-C10 cycloalkyl group or a C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; and
R6 and R7 are each a hydrogen atom;
or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.
2. The method according to claim 1, wherein, in the compound, R4 is a methyl group, or a pharmacologically acceptable salt thereof.
3. The method according to claim 2, wherein, in the compound, X is a group of a formula ═N—CH3, or a pharmacologically acceptable salt thereof.
4. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
5. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
6. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
7. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
8. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
9. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
10. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
11. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
12. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
13. The method according to claim 1, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
14. The method according to claim 1, wherein R1, R2 and R3 are each a hydrogen atom, R4 is a methyl group, n is 2 and Y-Z-R5 is —O—(CH2)3-(4-F-phenyl).
15. The method according to claim 1, wherein the compound is selected from the group consisting of
2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; and
a compound of the formula (Ia), wherein R1, R2 and R3 are each a hydrogen atom, R4 is a methyl group, n is 2 and Y-Z-R5 is —CO—(CH2)3-(4-F-phenyl),
or a pharmacologically acceptable salt thereof.
16. The method according to claim 4, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
17. The method according to claim 5, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
18. The method according to claim 6, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
19. The method according to claim 7, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
20. The method according to claim 8, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
21. The method according to claim 9, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
22. The method according to claim 10, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
23. The method according to claim 11, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
24. The method according to claim 12, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
25. The method according to claim 13, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
26. The method according to claim 14, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
27. The method according to claim 1, wherein the disease is rheumatoid arthritis.
28. The method according to claim 1, wherein the disease is psoriasis.
29. A method for the prevention of a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a mammal in need thereof, which comprises administering to said mammal a pharmaceutically effective amount of a compound of formula (Ia)
wherein R1 and R2 are each a hydrogen atom;
R3 is a hydrogen atom;
R4 is a C1-C2 alkyl group;
n is 2;
X is=N-D, wherein D is a hydrogen atom, a C1-C4 alkyl group or a phenyl group;
Y is an ethylene group, an ethynylene group, a group of a formula —CO—CH2 or a phenylene group;
Z is an ethylene group or a trimethylene group;
R5is an unsubstituted C3-C10 cycloalkyl group, an unsubstituted C6-C10 aryl group, or a C3-C10 cycloalkyl group or a C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; and
R6 and R7 are each a hydrogen atom;
or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.
30. The method according to claim 29, wherein, in the compound, R4 is a methyl group, or a pharmacologically acceptable salt thereof.
31. The method according to claim 30, wherein, in the compound, X is a group of a formula ═N—CH3, or a pharmacologically acceptable salt thereof.
32. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
33. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
34. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.
35. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
36. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
37. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.
38. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
39. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
40. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
41. The method according to claim 29, wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
42. The method according to claim 29, wherein R1, R2 and R3 are each a hydrogen atom, R4 is a methyl group, n is 2 and Y-Z-R5 is —O—(CH2)3-(4-F-phenyl).
43. The method according to claim 29, wherein the compound is selected from the group consisting of
2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;
2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; and
a compound of the formula (Ia), wherein R1, R2 and R3 are each a hydrogen atom, R4 is a methyl group, n is 2 and Y-Z-R5 is —O—(CH2)3-(4-F-phenyl),
or a pharmacologically acceptable salt thereof.
44. The method according to claim 32, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
45. The method according to claim 33, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
46. The method according to claim 34, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
47. The method according to claim 35, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
48. The method according to claim 36, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
49. The method according to claim 37, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
50. The method according to claim 38, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
51. The method according to claim 39, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
52. The method according to claim 40, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
53. The method according to claim 41, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
54. The method according to claim 42, wherein the configuration at the carbon atom to which the group of the formula —NR1R2 attaches is the R configuration, or a pharmacologically acceptable salt thereof.
55. The method according to claim 29, wherein the disease is rheumatoid arthritis.
56. The method according to claim 29, wherein the disease is psoriasis.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of application Ser. No. 10/889,657 filed Jul. 12, 2004, which is a continuation-in-part application of International application PCT/JP03/00136 filed Jan. 9, 2003, the entire contents of both of which are incorporated by reference herein.

TECHNICAL FIELD

The present invention relates to amino alcohol derivatives or phosphonic acid derivatives having excellent immunosuppressive activity, pharmacologically acceptable salts of amino alcohol derivatives or phosphonic acid derivatives, pharmacologically acceptable esters of amino alcohol derivatives or phosphonic acid derivatives, and to pharmaceutical compositions comprising said compounds as an active ingredient.

The present invention also relates to pharmaceutical compositions comprising, as active ingredients, one or more immunosuppressants and one or more compounds selected from the group consisting of amino alcohol derivatives or phosphonic acid derivatives having excellent immunosuppressive activity, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof. Said compositions are useful as preventive or therapeutic agents for autoimmune diseases such as rejection of transplanted tissues or cells, rheumatoid arthritis, or other immune activity-related autoimmune diseases.

BACKGROUND OF THE INVENTION

In the past, anti-inflammatory agents such as steroids have been used for inflammatory reactions arising from abnormal immune response in treatment of immune-related diseases such as rheumatoid arthritis and other autoimmune diseases. These are, however, a symptomatic therapy, but not a fundamental remedy.

Furthermore, it has been reported that immune system abnormalities are also involved in the development of diabetes and nephritis, but agents that improve these abnormalities have not yet been developed.

On the other hand, it is critical to develop an approach to suppress the immune response for avoiding rejection in transplanted tissues or cells, as well as for treating and preventing various autoimmune diseases.

However, immunosuppressants, such as cyclosporin A (CsA) and tacrolimus (TRL) that have been known in the past, are known to show toxicity against the kidney and liver. Although treatments that also use steroids are commonly used for the relief of such adverse reactions, it is presently the case that such agents have not necessarily led to producing a satisfactory immunosuppressive effect without showing any adverse reaction.

In light of this background, it has been attempted to find excellent compounds with immunosuppressive effects that are less toxic.

As to immunosuppressants, the following compounds are known.

  • (1) Compounds having the general formula (a) disclosed in WO 94/08943 (page 371)
    {in the above compounds (a),

Rx represents a straight or branched carbon chain which may optionally be substituted with one or more substituents [said chain may contain a double bond, a triple bond, an oxygen atom, a sulfur atom, a group of formula —N(Rx 6)— (wherein Rx 6 represents a hydrogen atom), an arylene group which may optionally be substituted with one or more substituents, or a heteroarylene group which may optionally be substituted with one or more substituents, and may contain, at the end of said chain, an aryl group which may optionally be substituted with one or more substituents, a cycloalkyl group which may optionally be substituted with one or more substituents, or an aromatic heterocyclic group which may optionally be substituted with one or more substituents], and

Rx 2, Rx 3, Rx 4, and Rx 5 are the same or different and each represents a hydrogen atom or an alkyl group] are known as immunosuppressants.

The above compounds (a) of the prior art contain two oxymethyl groups (—CH2ORx 4 and —CH2ORx 5) as essential groups substituted on the same carbon atom. The compounds of the present invention, however, contain one —CH2OR3 group and one lower alkyl group as essential groups substituted on the same carbon atom and are different from the compounds (a) in these substituents.

  • (2) Compounds having the general formula (b) disclosed in WO 96/06068 (page 271)
    [in the above compounds (b),

Ry 1, Ry 2, and Ry 3 each represent a hydrogen atom or the like, W represents a hydrogen atom, an alkyl group or the like, Zy represents a single bond or an alkylene group, Xy represents a hydrogen atom or an alkoxy group, and Yy represents a hydrogen atom, an alkyl, alkoxy, acyl, acyloxy, amino, acylamino group or the like] are known as immunosuppressants.

The above compounds (b) contain a phenyl group as an essential group in the basic skeleton. The compounds of the present invention contain a heterocyclic group such as a furyl group, a pyrrolyl group, or a pyrrolyl group having a substituent on the nitrogen atom instead of the phenyl group of compounds (b) and are different from the compounds (b).

However, compounds having a similar chemical structure to compounds (I) of the present invention have heretofore not been disclosed concretely in that publication.

  • (3) Compounds having the general formula (c) disclosed in WO 98/45249
    [in the above compounds (c),

Rz 1, Rz 2, Rz 3, and Rz 4 are the same or different and each represents a hydrogen atom or an acyl group] are known as immunosuppressants.

The above compounds (c) contain two oxymethyl groups (—CH2ORz 3 and —CH2ORz 4) as essential groups substituted on the same carbon atom. The compounds of the present invention, however, contain one —CH2OR3 group and one lower alkyl group as essential groups substituted on the same carbon atom and are different from the compounds (c) in these substituents.

In addition, above compounds (c) contain a phenyl group between the —(CH2)2— group and the —CO—(CH2)4 group as an essential group in the basic skeleton. The compounds of the present invention contain a heterocyclic group such as a furyl group, a pyrrolyl group, or a pyrrolyl group having a substituent on the nitrogen atom instead of the phenyl group of compound (c) and are different from the compounds (c).

On the other hand, a compound having the general formula (II) of the present invention shown below wherein X represents a sulfur atom is disclosed in WO 02/06268 as a compound wherein the protecting group of the hydroxyl group is a residual group of an ester of phosphoric acid.

Furthermore, as to combinations of immunosuppressants, combinations of immunosuppressants such as FTY-720 and cyclosporin A or FTY-720 and tacrolimus are disclosed in Japanese Patent Publication (Kokai) Number Hei 11-80026.

In light of this background, it has been desired to find excellent pharmaceutical compositions with immunosuppressive effects that are less toxic.

SUMMARY OF THE INVENTION

The present inventors have eagerly studied new compounds having excellent immunosuppressive activity with low toxicity and found new compounds which are useful as preventive or therapeutic agents for autoimmune diseases or other immunology-related diseases such as rejection caused by trans-plantation of various organs or skin, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, fibrositis, skeletal muscle inflammation, arthrosteitis, osteoarthritis, dermatomyositis, scleoderma, Behcet's syndrome, Crohn's disease, ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, multiple sclerosis, autoimmune bullosis, psoriasis vulgaris, vasculitis syndrome, Wegener's granuloma, uveitis, Sjögren's syndrome, idiopathic interstitial pneumonia, Goodpasture's syndrome, sarcoidosis, allergic granulomatous angitis, bronchial asthma, myocarditis, cardiomyopathy, aortitis syndrome, post myocardial infarction syndrome, primary pulmonary hypertension, minimal change nephrotic syndrome, membranous nephropathy, membranoproliferative glomerulone-phritis, focal glomerular sclerosis, crescentic glomerulone-phritis, myasthenia gravis, inflammatory neuropathy, atopic dermatitis, chronic actinic dermatitis, photosensitivity, pressure sores, Sydenham's chorea, sclerosis, adult-onset type diabetes mellitus, insulin dependent diabetes mellitus, juvenile diabetes mellitus, atherosclerosis, glomerular nephritis, IgA nephropathy, tubulointerstitial nephritis, primary biliary cirrhosis, primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis, GVHD, contact dermatitis, and sepsis; diseases of infection by fungus, mycoplasma, virus, and protozoan and the like; cardiovascular diseases such as cardiac failure, cardiac hypertrophy, arrhythmia, angina pectoris, cardiac ischemia, arterial embolism, aneurysm, varix, and circulation disorders; brain diseases such as Alzheimer's disease, dementia, Parkinson's disease, stroke, brain infarction, brain ischemia, depression, manic-depressive illness, schizo-phrenia, Huntington's chorea, epilepsy, convulsion, attention deficit disorder, encephalitis, cerebral meningitis, loss of appetite, and hyperphagia; and various diseases such as lymphoma, leukemia, diuresis, pollakisuria, and diabetic retinopathy (particularly, autoimmune diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rhematoid arthritis, multiple sclerosis, and atopic dermatitis), and completed the present invention.

Furthermore, the present inventors have studied eagerly pharmaceutical compositions having immunosuppressive activity and found that the pharmaceutical compositions of the present invention comprising, as active ingredients, one or more immunosuppressants and one or more compounds of the present invention exhibit excellent immunosuppressive activity with low toxicity. The pharmaceutical compositions increase activity more than that of the individual immunosuppressants and decrease adverse reactions so that they are less than that of the individual immunosuppressants. As a result, the pharmaceutical compositions of the present invention are useful as preventive or therapeutic agents for autoimmune diseases or other immunology-related diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, fibrositis, skeletal muscle inflammation, arthrosteitis, osteoarthritis, dermatomyositis, scleoderma, Behcet's syndrome, Crohn's disease, ulcerative colitis, autoimmune hepatitis, aplastic anemia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, multiple sclerosis, autoimmune bullosis, psoriasis vulgaris, vasculitis syndrome, Wegener's granuloma, uveitis, Sjögren's syndrome, idiopathic interstitial pneumonia, Goodpasture's syndrome, sarcoidosis, allergic granulomatous angitis, bronchial asthma, myocarditis, cardiomyopathy, aortitis syndrome, post myocardial infarction syndrome, primary pulmonary hypertension, minimal change nephrotic syndrome, membranous nephropathy, membranoproliferative glomerulonephritis, focal glomerular sclerosis, crescentic glomerulonephritis, myasthenia gravis, inflammatory neuropathy, atopic dermatitis, chronic actinic dermatitis, photosensitivity, pressure sores, Sydenham's chorea, sclerosis, adult-onset type diabetes mellitus, insulin dependent diabetes mellitus, juvenile diabetes mellitus, atherosclerosis, glomerular nephritis, IgA nephropathy, tubulointerstitial nephritis, primary biliary cirrhosis, primary sclerosing cholangitis, fulminant hepatitis, viral hepatitis, GVHD, contact dermatitis, and sepsis; diseases of infection by fungus, mycoplasma, virus, and protozoan and the like; cardiovascular diseases such as cardiac failure, cardiac hypertrophy, arrhythmia, angina pectoris, cardiac ischemia, arterial embolism, aneurysm, varix, and circulation disorders; brain diseases such as Alzheimer's disease, dementia, Parkinson's disease, stroke, brain infarction, brain ischemia, depression, manic-depressive illness, schizophrenia, Huntington's chorea, epilepsy, convulsion, attention deficit disorder, encephalitis, cerebral meningitis, loss of appetite, and hyperphagia; and various diseases such as lymphoma, leukemia, diuresis, pollakisuria, and diabetic retinopathy (particularly, autoimmune diseases such as rejection caused by transplantation of various organs or skin, systemic lupus erythematosus, rhematoid arthritis, multiple sclerosis, and atopic dermatitis) and the present inventors completed the present invention.

The present invention is explained in detail.

  • (1) Amino alcohol derivatives of the present invention are compounds of the general formula (I) shown below:
    [wherein,

R1 and R2 are the same or different and each represents a hydrogen atom, a lower alkyl group, or a protecting group of the amino group;

R3 represents a hydrogen atom, a lower alkyl group, or a protecting group of the hydroxyl group;

R4 represents a lower alkyl group;

n represents an integer of from 1 to 6;

X represents an oxygen atom or a group of formula ═N-D (wherein D represents a hydrogen atom, a C6-C10 aryl group, a lower alkylsulfonyl group, a C6-C10 arylsulfonyl group, or a group selected from Substituent group (a));

Y represents an ethylene group, a vinylene group, an ethynylene group, a group of formula: -E-CH2— (wherein E represents a carbonyl group or a group of formula: —CH(OH)—), a C6-C10 arylene group, or a C6-C10 arylene group substituted with from 1 to 3 substituents selected from Substituent group (a);

Z represents a single bond, a C1-C10 alkylene group, a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from Substituent group (a) and Substituent group (b), a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain;

R5 represents a hydrogen atom, a C3-C10 cycloalkyl group, a C6-C10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a 5- to 7-membered heterocyclic group containing .from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a) and Substituent group (b);

R6 and R7 are the same or different and each represents a hydrogen atom or a group selected from Substituent group (a);

Substituent group (a) represents the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a mono-lower alkylamino group, a di-lower alkylamino group, a lower aliphatic acylamino group, a cyano group, and a nitro group; and

Substituent group (b) represents the group consisting of a C3-C10 cycloalkyl group, a C6-C10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from Substituent group (a), a C6-C10 aryl group substituted with from 1 to 3 substituents selected from Substituent group (a), and a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a);

  • provided that when R5 represents a hydrogen atom, then Z represents a branched chain C1-C10 alkylene group, a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain].

The present invention provides compounds of formula (I), pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof.

Of these, preferred compounds are:

  • (2) a compound according to (1) wherein said compound of formula (I) has the formula (Ia):
    (wherein, R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as those indicated hereinbefore), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof,
  • (3) a compound according to (1) wherein said compound of formula (I) has the formula (Ib):
    (wherein, R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as those indicated hereinbefore), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof,
  • (4) a pharmacologically acceptable ester of the compound of formula (I) according to (1) wherein said compound of formula (I) has the formula (II):
    (wherein, R1, R2, R4, R5, R6, R7, X, Y, Z and n have the samemeanings as those indicated hereinbefore; R10 and R11 are the same or different and each represents a hydrogen atom or a protecting group of phosphoric acid), or a pharmacologically acceptable salt thereof,
  • (5) a pharmacologically acceptable ester of the compound of formula (II) according to (4) wherein said ester of formula (II) has the formula (IIa):
    (wherein, R1, R2, R4, R5, R6, R7, X, Y, Z and n have the same meanings as those indicated hereinbefore; R10 and R11 are the same or different and each represents a hydrogen atom or a protecting group of phosphoric acid), or a pharmacologically acceptable salt thereof, and
  • (6) a pharmacologically acceptable ester of the compound of formula (II) according to (4) wherein said ester of formula (II) has the formula (IIb):
    (wherein, R1, R2, R4, R5, R6, R7, X, Y, Z and n have the same meanings as those indicated hereinbefore; R10 and R11 are the same or different and each represents a hydrogen atom or a protecting group of phosphoric acid), or a pharmacologically acceptable salt thereof.
  • (7) Phosphonic acid derivatives of the present invention are compounds of the general formula (III) shown below:
    (wherein, R1, R2 R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore).

The present invention provides compounds of formula (III), pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof.

Of these, preferred compounds are:

  • (8) a compound according to (7) wherein said compound of formula (III) has the formula (IIIa):
    (wherein, R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof, and
  • (9) a compound according to (7) wherein said compound of formula (III) has the formula (IIIb):
    (wherein, R1, R2R3, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.
DETAILED DESCRIPTION OF THE INVENTION

Of these, preferred compounds are:

  • (10) a compound according to any one of (1) to (9) wherein R1 and R2 are the same or different and each represents a hydrogen atom, a lower aliphatic acyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or an aralkyloxycarbonyl group substituted with from 1 to 3 substituents selected from Substituent group (a), or a pharmacologically acceptable salt thereof,
  • (11) a compound according to any one of (1) to (9) wherein R1 and R2 are the same or different and each represents a hydrogen atom, a lower aliphatic acyl group, or a lower alkoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (12) a compound according to any one of (1) to (9) wherein R1 and R2 are the same or different and each represents a hydrogen atom, a C1-C4 aliphatic acyl group, or a C1-C4 alkoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (13) a compound according to any one of (1) to (9) wherein R1 and R2 are the same or different and each represents a hydrogenatom, a C1-C2 aliphatic acyl group, or a C1-C2 alkoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (14) a compound according to any one of (1) to (9) wherein R1 and R2 are the same or different and each represents a hydrogen atom, an acetyl group, or a methoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (15) a compound according to any one of (1) to (9) wherein each of R1 and R2 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (16) a compound according to any one of (1) to (3) and (10) to (15) wherein R3 represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, an aromatic acyl group, an aromatic acyl group substituted with from 1 to 3 substituents selected from Substituent group (a), or a silyl group, or a pharmacologically acceptable salt thereof,
  • (17) a compound according to any one of (1) to (3) and (10) to (15) wherein R3 represents a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt thereof,
  • (18) a compound according to any one of (1) to (3) and (10) to (15) wherein R3 represents a hydrogen atom or a C1-C4 alkyl group, or a pharmacologically acceptable salt thereof,
  • (19) a compound according to any one of (1) to (3) and (10) to (15) wherein R3 represents a hydrogen atom, a methyl group, or an ethyl group, or a pharmacologically acceptable salt thereof,
  • (20) a compound according to any one of (1) to (3) and (10) to (15) wherein R3 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (21) a compound according to any one of (1) to (20) wherein R4 represents a C1-C4 alkyl group, or a pharmacologically acceptable salt thereof,
  • (22) a compound according to any one of (1) to (20) wherein R4 represents a C1-C2 alkyl group, or a pharmacologically acceptable salt thereof,
  • (23) a compound according to any one of (1) to (20) wherein R4 represents a methyl group, or a pharmacologically acceptable salt thereof,
  • (24) a compound according to any one of (1) to (23) wherein n represents an integer 2 or 3, or a pharmacologically acceptable salt thereof,
  • (25) a compound according to any one of (1) to (23) wherein n represents an integer 2, or a pharmacologically acceptable salt thereof,
  • (26) a compound according to any one of (1) to (25) wherein X represents an oxygen atom, or a pharmacologically acceptable salt thereof,
  • (27) a compound according to any one of (1) to (25) wherein X represents a group of formula: ═N-D (wherein D represents a hydrogen atom, a C1-C4 alkyl group, or a phenyl group), or a pharmacologically acceptable salt thereof,
  • (28) a compound according to any one of (1) to (25) wherein X represents a group of formula: ═N—CH3, or a pharmacologically acceptable salt thereof,
  • (29) a compound according to any one of (1) to (28) wherein Y represents an ethylene group, an ethynylene group, a group of formula: —CO—CH2—, a group of formula: —CH(OH)—CH2—, aphenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group, or a pharmacologically acceptable salt thereof,
  • (30) a compound according to any one of (1) to (28) wherein Y represents an ethylene group, an ethynylene group, a group of formula: —CO—CH2—, or a phenylene group, or a pharmacologically acceptable salt thereof,
  • (31) a compound according to any one of (1) to (30) wherein Z represents a C1-C10 alkylene group or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a pharmacologically acceptable salt thereof,
  • (32) a compound according to any one of (1) to (30) wherein Z represents a C1-C6 alkylene group or a C1-C6 alkylene group substituted with from 1 to 3 hydroxyl groups, or a pharmacologically acceptable salt thereof,
  • (33) a compound according to any one of (1) to (30) wherein Z represents a C1-C5 alkylene group or a C1-C5 alkylene group substituted with from 1 to 3 hydroxyl groups, or a pharmacologically acceptable salt thereof,
  • (34) a compound according to any one of (1) to (30) wherein Z represents an ethylene group, a trimethylene group, a tetramethylene group, or an ethylene, trimethylene, or tetramethylene group substituted with one hydroxyl group, or a pharmacologically acceptable salt thereof,
  • (35) a compound according to any one of (1) to (30) wherein Z represents an ethylene group, a trimethylene group, or a tetramethylene group, or a pharmacologically acceptable salt thereof,
  • (36) a compound according to any one of (1) to (30) wherein Z represents an ethylene group or a trimethylene group, or a pharmacologically acceptable salt thereof,
  • (37) a compound according to any one of (1) to (30) wherein Z represents a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain or a C1-C10 alkylene group substituted with one substituent which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain (said substituent is selected from the group consisting of a lower alkyl group and a hydroxyl group), or a pharmacologically acceptable salt thereof,
  • (38) a compound according to any one of (1) to (30) wherein Z represents a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a pharmacologically acceptable salt thereof,
  • (39) a compound according to any one of (1) to (30) wherein Z represents a C1-C10 alkylene group which has an oxygen atom in said carbon chain or at the end of said carbon chain, or a pharmacologically acceptable salt thereof,
  • (40) a compound according to any one of (1) to (30) wherein Z represents a C1-C6 alkylene group which has an oxygen atom in said carbon chain or at the end of said carbon chain, or a pharmacologically acceptable salt thereof,
  • (41) a compound according to any one of (1) to (30) wherein Z represents a group of formula —O—CH2—, —O—(CH2)2—, —O—(CH2)3—, —CH2—O—, —(CH2)2—O—, or —(CH2)3—O—, or a pharmacologically acceptable salt thereof,
  • (42) a compound according to any one of (1) to (30) wherein Z represents a group of formula —CH2—O— or —(CH2)2—O—, or a pharmacologically acceptable salt thereof,
  • (43) a compound according to any one of (1) to (42) wherein R5 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (44) a compound according to any one of (1) to (42) wherein R5 represents a C3-C10 cycloalkyl group, a C6-C10 aryl group, or a C3-C10 cycloalkyl or C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, and a lower alkylthio group, or a pharmacologically acceptable salt thereof,
  • (45) a compound according to any one of (1) to (42) wherein R5 represents a C3-C10 cycloalkyl group, a C6-C10 aryl group, or a C3-C10 cycloalkyl or C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, and a lower alkoxy group, or a pharmacologically acceptable salt thereof,
  • (46) a compound according to any one of (1) to (42) wherein R5 represents a C5-C6 cycloalkyl group, a phenyl group, or a naphthyl group, or a pharmacologically acceptable salt thereof,
  • (47) a compound according to any one of (1) to (42) wherein R5 represents a cyclohexyl group or a phenyl group, or a pharmacologically acceptable salt thereof,
  • (48) a compound according to any one of (1) to (47) wherein R6 and R7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group, or a pharmacologically acceptable salt thereof,
  • (49) a compound according to any one of (1) to (47) wherein each of R6 and R7 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (50) a compound according to any one of (4) to (15) and (21) to (49) wherein R10 and R11 are the same or different and each represents a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt thereof,
  • (51) a compound according to any one of (4) to (15) and (21) to (49) wherein R10 and R11 are the same or different and each represents a hydrogen atom or a C1-C4 alkyl group, or a pharmacologically acceptable salt thereof,
  • (52) a compound according to any one of (4) to (15) and (21) 'to (49) wherein R10 and R11 are the same or different and each represents a hydrogen atom, a methyl group, or an ethyl group, or a pharmacologically acceptable salt thereof, and
  • (53) a compound according to any one of (4) to (15) and (21) to (49) wherein each of R10 and R11 represents a hydrogen atom, or a pharmacologically acceptable salt thereof.

Compounds according to (1) above which comprise any combination selected freely from the groups consisting of (2) and (3); (10) to (15); (16) to (20); (21) to (23); (24) and (25); (26) to (28); (29) and (30); (31) to (42); (43) to (47); and (48) and (49) are preferred.

Compounds according to (4) above which comprise any combination selected freely from the groups consisting of (5) and (6); (10) to (15); (21) to (23); (24) and (25); (26) to (28); (29) and (30); (31) to (42); (43) to (47); (48) and (49); and (50) to (53) are preferred.

Compounds according to (7) above which comprise any combination selected freely from the groups consisting of (8) and (9); (10) to (15); (21) to (23); (24) and (25); (26) to (28); (29) and (30); (31) to (42); (43) to (47); (48) and (49); and (50) to (53) are preferred.

Of these, the most preferred compounds are:

  • (54) a compound selected from the following compounds, a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof:
  • 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol, and
  • 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,
  • (55) a compound selected from the following compounds, a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof:
  • 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol, and
  • 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
  • (56) a compound according to (4) wherein said compound is selected from the following compounds or a pharmacologically acceptable salt thereof:
  • mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl phosphate, and
  • mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}-1-butyl phosphate,
  • (57) a compound according to (4) wherein said compound is selected from the following compounds or a pharmacologically acceptable salt thereof:
  • mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, and
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl phosphate.
  • (58) a compound according to (7) wherein said compound is selected from the following compounds or a pharmacologically acceptable salt thereof:
  • 3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic acid, and
  • 3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic acid, and
  • (59) a compound according to (7) wherein said compound is selected from the following compounds or a pharmacologically acceptable salt thereof:
  • 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic acid, and
  • 3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic acid.

Furthermore, the present invention provides the following pharmaceutical compositions:

  • (60) a pharmaceutical composition containing at least one immunosuppressant selected from the group consisting of an agent having the action of inhibiting intracellular signal transduction involved in cytokine expression of T-cells,
  • an agent having the action of inhibiting nucleoside synthesis in immune cells,
  • an agent having the action of inhibiting the action of cytokines on immune cells and having antirheumatic action,
  • an alkylating agent causing cell death by breakdown of DNA chains or blocking DNA synthesis,
  • a metabolic antagonist inhibiting the metabolism of nucleic acids by blocking folic acid production,
  • a protein drug having the suppression action of TNF-α,
  • a steroid hormone agent that binds to intracellular steroid receptors to form a complex which binds to reaction sites on chromosomes, resulting in the synthesis of proteins which show immunosuppressive activity,
  • a substance suppressing prostaglandin production and/or nonsteroidal anti-inflammatory drug antagonizing the action of prostaglandin, and
  • at least one compound selected from the group consisting of compounds of the general formula (I):
    [wherein,

R1 and R2 are the same or different and each represents a hydrogen atom, a lower alkyl group, or a protecting group of the amino group;

R3 represents a hydrogen atom, a lower alkyl group, or a protecting group of the hydroxyl group;

R4 represents a lower alkyl group;

n represents an integer of from 1 to 6;

X represents a sulfur atom, an oxygen atom, or a group of formula ═N-D (wherein D represents a hydrogen atom, an aryl group, a lower alkylsulfonyl group, an arylsulfonyl group, or a group selected from Substituent group (a));

Y represents an ethylene group, a vinylene group, an ethynylene group, a group of formula -E-CH2— (wherein E represents a carbonyl group or a group of formula —CH(OH)—), a C6-C10 arylene group, or a C6-C10 arylene group substituted with from 1 to 3 substituents selected from Substituent group (a);

Z represents a single bond, a C1-C10 alkylene group, a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at theend of said carbon chain, or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain;

R5 represents a hydrogen atom, a C3-C10 cycloalkyl group, a C6-C10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b);

R6 and R7 are the same or different and each represents a hydrogen atom or a group selected from Substituent group (a);

Substituent group (a) represents the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a mono-lower alkylamino group, a di-lower alkylamino group, a lower aliphatic acylamino group, a cyano group, and a nitro group; and

Substituent group (b) represents the group consisting of a C6-C10 cycloalkyl group, a C6-C10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from Substituent group (a), a C6-C10 aryl group substituted with from 1 to 3 substituents selected from Substituent group (a), and a 5- to 7-membered heterocyclic group containing from 1 to 3-heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a);

  • provided that when R5 represents a hydrogen atom, then Z represents a branched chain C1-C10 alkylene group, a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain],
  • a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.

Of these, preferred pharmaceutical compositions are:

  • (61) a pharmaceutical composition according to (60) wherein said compound of general formula (I) has the general formula (Ia) shown below:
    (wherein, R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the same meanings as those indicated hereinbefore),
  • (62) a pharmaceutical composition according to (60) wherein said compound of general formula (I) has the general formula (Ib) shown below:
    (wherein, R1, R2, R3, R4, R5, R6, R7, X, Y, Z and n have the samemeanings as those indicated hereinbefore),
  • (63) a pharmaceutical composition according to (60) wherein the pharmacologically acceptable ester of the compound of formula (I) has the formula (II):
    (wherein, R1, R2, R4, R5, R6, R7, X, Y, Z and n have the same meanings as those indicated hereinbefore; R10 and R11 are the same or different and each represents a hydrogen atom or a protecting group of phosphoric acid) or a pharmacologically acceptable salt thereof,
  • (64) a pharmaceutical composition according to (63) wherein the ester of the compound of formula (II) has the formula (IIa):
    (wherein, R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore) or a pharmacologically acceptable salt thereof, and
  • (65) a pharmaceutical composition according to (63) wherein the ester of the compound of formula (II) has the formula (IIb):
    (wherein, R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore) or a pharmacologically acceptable salt thereof.

Furthermore, the present invention provides the following pharmaceutical compositions:

  • (66) a pharmaceutical composition containing at least one immunosuppressant selected from the group consisting of an agent having the action of inhibiting intracellular signal transduction involved in cytokine expression of T-cells,
  • an agent having the action of inhibiting nucleoside synthesis in immune cells,
  • an agent having the action of inhibiting the action of cytokines on immune cells and having antirheumatic action,
  • an alkylating agent causing cell death by breakdown of DNA chains or blocking DNA synthesis,
  • a metabolic antagonist inhibiting the metabolism of nucleic acids by blocking folic acid production,
  • a protein drug having the suppression action of TNF-α,
  • a steroid hormone agent that binds to intracellular steroid receptors to form a complex which binds to reaction sites on chromosomes, resulting in the synthesis of proteins which show immunosuppressive activity, and
  • a substance suppressing prostaglandin production and/or nonsteroidal anti-inflammatory drug antagonizing the action of prostaglandin, and
  • at least one compound selected from the group consisting of compounds of the general formula (III) shown below:
    [wherein,

R1 and R2 are the same or different and each represents a hydrogen atom, a lower alkyl group, or a protecting group of the amino group;

R4 represents a lower alkyl group;

n represents an integer of from 1 to 6;

X represents a sulfur atom, an oxygen atom or a group of formula ═N-D (wherein D represents a hydrogen atom, a C6-C10 aryl group, a lower alkylsulfonyl group, a C6-C10 arylsulfonyl group, or a group selected from Substituent group (a));

Y represents an ethylene group, a vinylene group, an ethynylene group, a group of formula -E-CH2— (wherein E represents a carbonyl group or a group of formula —CH(OH)—), a C6-C10 arylene group, or a C6-C10 arylene group substituted with from 1 to 3 substituents selected from Substituent group (a);

Z represents a single bond, a C1-C10 alkylene group, a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain;

R represents a hydrogen atom, a C3-C10 cycloalkyl group, a C6-C10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b);

R6 and R7 are the same or different and each represents a hydrogen atom or a group'selected from Substituent group (a);

R10 and R11 are the same or different and each represents a hydrogen atom or a protecting group of phosphoric acid;

Substituent group (a) represents the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a mono-lower alkylamino group, a di-lower alkylamino group, a lower aliphatic acylamino group, a cyano group, and a nitro group; and

Substituent group (b) represents the group consisting of a C3-C10 cycloalkyl group, a C6-C10 aryl group, a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom, a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from Substituent group (a), a C6-C10 aryl group substituted with from 1 to 3 substituents selected from Substituent group (a), and a 5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a);

  • provided that when R5 represents a hydrogen atom, then Z represents a branched chain C1-C10 alkylene group, a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain],
  • a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.

Of these, preferred pharmaceutical compositions are:

  • (67) a pharmaceutical composition according to (66) wherein the compound of formula (III) has the formula (IIIa):
    (wherein, R1, R2, R4, R5, R6, R7, R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore), and
  • (68) a pharmaceutical composition according to (66) wherein the compound of formula (III) has the formula (IIIb)
    (wherein, R1, R2, R4, R5, R6, R7R10, R11, X, Y, Z and n have the same meanings as those indicated hereinbefore).

Of these, more preferred pharmaceutical compositions are:

  • (69) a pharmaceutical composition according to any one of (60) to (68) containing a compound wherein R1 and R2 are the same or different and each represents a hydrogen atom, a lower aliphatic acyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or an aralkyloxycarbonyl group substituted with from 1 to 3 substituents selected from Substituent group (a), or a pharmacologically acceptable salt thereof,
  • (70) a pharmaceutical composition according to any one of (60) to (68) containing a compound wherein R1 and R2 are the same or different and each represents a hydrogen atom, a lower aliphatic acyl group, or a lower alkoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (71) a pharmaceutical composition according to any one of (60) to (68) containing a compound wherein R1 and R2 are the same or different and each represents a hydrogen atom, a C1-C4 aliphatic acyl group, or a C1-C4 alkoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (72) a pharmaceutical composition according to any one of (60) to (68) containing a compound wherein R1 and R2 are the same or different and each represents a hydrogen atom, a C1-C2 aliphatic acyl group, or a C1-C2 alkoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (73) a pharmaceutical composition according to any one of (60) to (68) containing a compound wherein R1 and R2 are the same or different and each represents a hydrogen atom, an acetyl group, or a methoxycarbonyl group, or a pharmacologically acceptable salt thereof,
  • (74) a pharmaceutical composition according to any one of (60) to (68) containing a compound wherein each of R1 and R2 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (75) a pharmaceutical composition according to any one of (60) to (62) and (69) to (74) containing a compound wherein R3 represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, an aromatic acyl group, an aromatic acyl group substituted with from 1 to 3 substituents selected from Substituent group (a), or a silyl group, or a pharmacologically acceptable salt thereof,
  • (76) a pharmaceutical composition according to any one of (60) to (62) and (69) to (74) containing a compound wherein R3 represents a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt thereof,
  • (77) a pharmaceutical composition according to any one of (60) to (62) and (69) to (74) containing a compound wherein R3 represents a hydrogen atom or a C1-C4 alkyl group, or a pharmacologically acceptable salt thereof,
  • (78) a pharmaceutical composition according to any one of (60) to (62) and (69) to (74) containing a compound wherein R3 represents a hydrogen atom, a methyl group, or an ethyl group, or a pharmacologically acceptable salt thereof,
  • (79) a pharmaceutical composition according to any one of (60) to (62) and (69) to (74) containing a compound wherein R3 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (80) a pharmaceutical composition according to any one of (60) to (79) containing a compound wherein R4 represents a C1-C4 alkyl group, or a pharmacologically acceptable salt thereof.
  • (81) a pharmaceutical composition according to any one of (60) to (79) containing a compound wherein R4 represents a C1-C2 alkyl group, or a pharmacologically acceptable salt thereof,
  • (82) a pharmaceutical composition according to any one of (60) to (79) containing a compound wherein R4 represents a methyl group, or a pharmacologically acceptable salt thereof,
  • (83) a pharmaceutical composition according to any one of (60) to (82) containing a compound wherein n represents an integer 2 or 3, or a pharmacologically acceptable salt thereof,
  • (84) a pharmaceutical composition according to any one of (60) to (82) containing a compound wherein n represents an integer 2, or a pharmacologically acceptable salt thereof,
  • (85) a pharmaceutical composition according to any one of (60) to (84) containing a compound wherein X represents a sulfur atom, or a pharmacologically acceptable salt thereof,
  • (86) a pharmaceutical composition according to any one of (60) to (84) containing a compound wherein X represents an oxygen atom, or a pharmacologically acceptable salt thereof,
    • (87) a pharmaceutical composition according to any one of (60) to (84) containing a compound wherein X represents a group of formula ═N-D (wherein D represents a hydrogen atom, a C1-C4 alkyl group, or a phenyl group), or a pharmacologicallyacceptable salt thereof,
  • (88) a pharmaceutical composition according to any one of (60) to (84) containing a compound wherein X represents a group of formula ═N—CH3, or a pharmacologically acceptable salt thereof,
  • (89) a pharmaceutical composition according to any one of (60) to (88) containing a compound wherein Y represents an ethylene group, an ethynylene group, a group of formula —CO—CH2—, a group of formula —CH(OH)—CH2—, a phenylene group, or a phenylene group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group, or a pharmacologically acceptable salt thereof,
  • (90) a pharmaceutical composition according to any one of (60) to (88) containing a compound wherein Y represents an ethylene group, an ethynylene group, a group of formula —CO—CH2—, or a phenylene group, or a pharmacologically acceptable salt thereof,
  • (91) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C10 alkylene group or a C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b), or a pharmacologically acceptable salt thereof,
  • (92) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C6 alkylene group or a C1-C6 alkylene group substituted with from 1 to 3 hydroxyl groups, or a pharmacologically acceptable salt thereof,
  • (93) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C5 alkylene group or a C1-C5 alkylene group substituted with from1 to 3 hydroxyl groups, or a pharmacologically acceptable salt thereof,
  • (94) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents an ethylene group, a trimethylene group, a tetramethylene group, or an ethylene, trimethylene, or tetramethylene group substituted with one hydroxyl group, or a pharmacologically acceptable salt thereof,
  • (95) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents an ethylene group, a trimethylene group, or a tetramethylene group, or a pharmacologically acceptable salt thereof,
  • (96) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents an ethylene group or a trimethylene group, or a pharmacologically acceptable salt thereof,
  • (97) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain or a C1-C10 alkylene group substituted with one substituent which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain (said substituent is selected from the group consisting of lower alkyl groups and hydroxyl groups), or a pharmacologically acceptable salt thereof,
  • (98) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain, or a pharmacologically acceptable salt thereof,
  • (99) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C10 alkylene group which has an oxygen atom in said carbon chain or at the end of said carbon chain, or a pharmacologically acceptable salt thereof,
  • (100) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a C1-C6 alkylene group which has an oxygen atom in said carbon chain or at the end of said carbon chain, or a pharmacologically acceptable salt thereof,
  • (101) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a group of formula —O—CH2—, —O—(CH2)2—, —O—(CH2)3—, —CH2—O—, —(CH2)2—O—, or —(CH2)3—O—, or a pharmacologically acceptable salt thereof,
  • (102) a pharmaceutical composition according to any one of (60) to (90) containing a compound wherein Z represents a group of formula —CH2—O— or —(CH2)2—O—, or a pharmacologically acceptable salt thereof,
  • (103) a pharmaceutical composition according to any one of (60) to (102) containing a compound wherein R5 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (104) a pharmaceutical composition according to any one of (60) to (102) containing a compound wherein R5 represents a C3-C10 cycloalkyl group, a C6-C10 aryl group, or a C3-C10 cycloalkyl or C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, and a lower alkylthio group, or a pharmacologically acceptable salt thereof,
  • (105) a pharmaceutical composition according to any one of (60) to (102) containing a compound wherein R5 represents a C3-C10 cycloalkyl group, a C6-C10 aryl group, or a C3-C10 cycloalkyl or C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group, and a lower alkoxy group, or a pharmacologically acceptable salt thereof,
  • (106) a pharmaceutical composition according to any one of (60) to (102) containing a compound wherein R5 represents a C5-C6 cycloalkyl group, a phenyl group, or a naphthyl group, or a pharmacologically acceptable salt thereof,
  • (107) a pharmaceutical composition according to any one of (60) to (102) containing a compound wherein R5 represents a cyclohexyl group or a phenyl group, or a pharmacologically acceptable salt thereof,
  • (108) a pharmaceutical composition according to any one of (60) to (107) containing a compound wherein R6 and R7 are the same or different and each represents a hydrogen atom, a halogen atom, a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, or a lower alkylthio group, or a pharmacologically acceptable salt thereof,
  • (109) a pharmaceutical composition according to any one of (60) to (107) containing a compound wherein each of R6 and R7 represents a hydrogen atom, or a pharmacologically acceptable salt thereof,
  • (110) a pharmaceutical composition according to any one of (63) to (74) and (80) to (109) containing a compound wherein R10 and R11 are the same or different and each represents a hydrogen atom or a lower alkyl group, or a pharmacologically acceptable salt thereof,
  • (111) a pharmaceutical composition according to any one of (63) to (74) and (80) to (109) containing a compound wherein R10 and R11 are the same or different and each represents a hydrogen atom or a C1-C4 alkyl group, or a pharmacologically acceptable salt thereof,
  • (112) a pharmaceutical composition according to any one of (63) to (74) and (80) to (109) containing a compound wherein R10 and R11 are the same or different and each represents a hydrogen atom, a methyl group or an ethyl group, or a pharmacologically acceptable salt thereof, and
  • (113) a pharmaceutical composition according to any one of (63) to (74) and (80) to (109) containing a compound whereineach of R10 and R11 represents a hydrogen atom, or a pharmacologically acceptable salt thereof.

Of these, particularly preferred pharmaceutical compositions are:

  • (114) a pharmaceutical composition according to (60), wherein the compound of general formula (I), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • 2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}butan-1-ol
  • 2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[5-(3-cyclohexylmethoxyprop-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol, and
  • 2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}butan-1-ol,
  • (115) a pharmaceutical composition according to (60), wherein the compound of general formula (I), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]butan-1-ol, and
  • 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}butan-1-ol,
  • (116) a pharmaceutical composition according to (60), whereinthe compound of general formula (I), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(5-cyclhexylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]butan-1-ol, and
  • 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylpenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl }butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol,
  • 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.
  • (117) a pharmaceutical composition according to (63), wherein the compound of general formula (II), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexylbutyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-benzyloxybutyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(3-cyclohexylmethoxy)prop-1-ynyl]thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-phenylbutanoyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpentyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-ethyl-4-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate, and
  • mono 2-amino-2-methyl-4-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}-1-butyl phosphate,
  • (118) a pharmaceutical composition according to (63), wherein the compound of general formula (II), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • mono 2-amino-2-methyl-4-[5-(5-phenylpentyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-phenylpent-1-ynyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[5-(5-cyclohexylpentanoyl)furan-2-yl]-1-butyl phosphate, and
  • mono 2-amino-2-methyl-4-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}-1-butyl phosphate,
  • (119) a pharmaceutical composition according to (63), wherein the compound of general formula (II), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]-1-butyl phosphate, and
  • mono 2-amino-2-methyl-4-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl phosphate,
  • mono 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}-1-butyl phosphate.
  • (120) a pharmaceutical composition according to (66), wherein the compound of general formula (III), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • 3-amino-3-methyl-5-[5-(4-cyclohexylbutyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-phenylpentyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-cyclohexyloxybutyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)butyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[4-(4-methoxyphenoxy)butyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-benzyloxybutyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-cyclohexylbut-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-phenylbut-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pent-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[5-(4-methoxyphenyl)pent-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(4-methylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(4-ethylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(4-methylthiophenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[4-(4-fluorophenoxy)but-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[4-(4-methylphenoxy)but-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(3-cyclohexylmethoxy)prop-1-ynyl]thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-benzyloxybut-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-cyclohexylbutanoyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-phenylbutanoyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-phenylpentanoyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[5-(4-fluorophenyl)pentanoyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-ethyl-5-[5-(5-cyclohexylpentyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-ethyl-5-[5-(5-cyclohexylpent-1-ynyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-ethyl-5-[5-(5-cyclohexylpentanoyl)thiophen-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(4-chlorophenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(3-methylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(3-methoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(3,4-dimethoxyphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(3,5-dimethoxyphenoxyl)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-{5-[3-(3-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid, and
  • 3-amino-3-methyl-5-{5-[3-(4-acetylphenoxy)prop-1-ynyl]thiophen-2-yl}pentylphosphonic acid,
  • (121) a pharmaceutical composition according to (66), wherein the compound of general formula (III), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • 3-amino-3-methyl-5-[5-(5-phenylpentyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpent-1-ynyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-phenylpent-1-ynyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(4-cyclohexyloxybut-1-ynyl)furan-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[5-(5-cyclohexylpentanoyl)furan-2-yl]pentylphosphonic acid, and
  • 3-amino-3-methyl-5-{5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]furan-2-yl}pentylphosphonic acid,
  • (122) a pharmaceutical composition according to (66), wherein the compound of general formula (III), or pharmacologically acceptable salt thereof, or pharmacologically acceptable ester thereof is selected from the group consisting of the compounds described below, pharmacologically acceptable salts thereof, and pharmacologically acceptable esters thereof:
  • 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpent-1-ynyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{1-methyl-5-[3-(4-methylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexyloxybut-1-ynyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-{1-methyl-5-[3-(3,4-dimethylphenoxy)prop-1-ynyl]pyrrol-2-yl}pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-methyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-ethyl-5-(5-phenylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-ethyl-5-(5-cyclohexylpentanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • 3-amino-3-methyl-5-[1-ethyl-5-(4-phenylbutanoyl)pyrrol-2-yl]pentylphosphonic acid, and
  • 3-amino-3-methyl-5-[1-ethyl-5-(4-cyclohexylbutanoyl)pyrrol-2-yl]pentylphosphonic acid,
  • (123) a pharmaceutical composition according to any one of (60) to (122) wherein said composition contains at least one immunosuppressant selected from the group consisting of agents having the action of inhibiting intracellular signal transduction involved in cytokine expression of T-cells (said agents are cyclosporin A, tacrolimus, rapamycin, gusperimus, everolimus, tresperimus, anisperimus, SDZ-281-240, ABT-281, tigderimus, A-119435, or 17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone),
  • agents having the action of inhibiting nucleoside synthesis in immune cells (said agents are mizoribine, azathioprine, mycophenolate Mofetil, leflunomide, merimempodib, HMR-1279, TSK-204, or SP-100030),
  • agents having the action of inhibiting the action of cytokines on immune cells and having antirheumatic action (said agents are T-614, actarit, salazosulfapyridine, or CDC-801), alkylating agents causing cell death by breakdown of DNA chains or blocking DNA synthesis (said alkylating agent is cyclophosphamide),
  • metabolic antagonists inhibiting the metabolism of nucleic acids by blocking folic acid production (said metabolic antagonist is methotrexate),
  • protein drugs having the suppression action of TNF-α (said protein drugs are remicade, enbrel, daclizumab, basiliximab, alemtuzumab, omalizumab, BMS-188667, CDP-571, inolimomab, ATM-027, or BTI-322),
  • steroid hormone agents that bind to intracellular steroid receptors to form a complex which binds to reaction sites on chromosomes, resulting in the synthesis of proteins which show immunosuppressive activity (said steroid hormone agent is prednisolone), and
  • substances suppressing prostaglandin production and/or nonsteroidal anti-inflammatory drugs antagonizing the action of prostaglandin (said nonsteroidal anti-inflammatory drugs are loxoprofen sodium, diclofenac sodium, meloxicam, celecoxib, or rofecoxib), and
  • (124) a pharmaceutical composition according to any one of (60) to (122) wherein said composition contains at least one immunosuppressant selected from the group consisting of cyclosporin A, tacrolimus, rapamycin, leflunomide,methotrexate, remicade, and enbrel.

Another object of the present invention is to provide the following pharmaceutical compositions and methods:

  • (125) a pharmaceutical composition comprising as an active ingredient a compound, a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof according to any one of (1) to (59),
  • (126) a pharmaceutical composition according to (125) for the prevention or treatment of autoimmune diseases,
  • (127) a pharmaceutical composition according to (126) wherein said autoimmune disease is rheumatoid arthritis,
  • a pharmaceutical composition according to (126) wherein said autoimmune disease is Crohn's disease or ulcerative colitis,
  • a pharmaceutical composition according to (126) wherein said autoimmune disease is multiple sclerosis,
  • a pharmaceutical composition according to (126) wherein said autoimmune disease is psoriasis,
  • a pharmaceutical composition according to (126) wherein said autoimmune disease is atopic dermatitis,
  • a pharmaceutical composition according to (126) wherein said autoimmune disease is insulin dependent diabetes mellitus,
  • a pharmaceutical composition according to (126) wherein said autoimmune disease is glomerular nephritis,
  • (128) a pharmaceutical composition according to (125) for suppression of rejection caused by transplantation of various organs or skin,
  • (129) a method for the prevention or treatment of autoimmune diseases in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of (60) to (125),
  • (130) a method for the prevention or treatment of rheumatoid arthritis in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of (60) to (125), and
  • a method for the prevention or treatment of psoriasis in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of (60) to (125),
  • a method for the prevention or treatment of Crohn's disease or ulcerative colitis in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of (60) to (125),
  • a method for the prevention or treatment of multiple sclerosis in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of (60) to (125),
  • a method for the prevention or treatment of atopic dermatitis in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of claims 60 to 125.
  • a method for the prevention or treatment of insulin dependent diabetes mellitus in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of claims 60 to 125.
  • a method for the prevention or treatment of glomerular nephritis in a mammal which comprises administering to said mammal an effective amount of a pharmaceutical composition according to any one of claims 60 to 125.
  • (131) a method for the prevention or treatment of rejection caused by transplantation of various organs or skin in a mammal which comprises administering to said mammal aneffective amount of a pharmaceutical composition according to any one of (60) to (125).

In the formulae (I), (II) and (III), the aryl moiety of the “C6-C10 aryl group”, the “C6-C10 aryl group which is substituted with from 1 to 3 substituents selected from Substituent group (a)”, or the “C6-C10 aryl group which is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) ” in the definition of D, R5 or Substituent group (b) can be, for example, a group such as a phenyl, indenyl, or naphthyl group, and is preferably a phenylene or naphthylene group, and most preferably a phenylene group.

The arylene moiety of the “C6-C10 arylene group”; the “C6-C10 arylene group which is substituted with from 1 to 3 substituents selected from Substituent group (a)”, or the “C6-C10 arylene group which is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b)” in the definition of Y or E can be, for example, a group such as a phenylene, indenylene, or naphthylene group, and is preferably a phenylene or naphthylene group, and most preferably a phenylene group.

The C1-C10 alkylene moiety of the “C1-C10 alkylene group” or the “C1-C10 alkylene group which is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b)”, in the definition of Z includes straight or branched chain alkylene groups having from 1 to 10 carbon atoms, and can be, for example, a group such as a methylene, methylmethylene, ethylene, propylene, trimethylene, 1-methylethylene, tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, 1-methylpropylene, 1,1-dimethylethylene, pentamethylene, 1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene, 4-methyltetramethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, hexamethylene, 1-methylpentamethylene, 2-methylpentamethylene, 3-methylpentamethylene, 4-methylpentamethylene, 5-methylpentamethylene, 1,1-dimethyltetramethylene, 2,2-dimethyltetramethylene, 3,3-dimethyltetramethylene, 4,4-dimethyltetramethylene, heptamethylene, 1-methylhexamethylene, 2-methylhexamethylene, 5-methylhexamethylene, 3-ethylpentamethylene, octamethylene, 2-methylheptamethylene, 5-methylheptamethylene, 2-ethylhexamethylene, 2-ethyl-3-methylpentamethylene, 3-ethyl-2-methylpentamethylene, nonamethylene, 2-methyloctamethylene, 7-methyloctamethylene, 4-ethylheptamethylene, 3-ethyl-2-methylhexamethylene, 2-ethyl-1-methylhexamethylene or decamethylene group, and is preferably a C1-C6 alkylene group, more preferably a C1-C5 alkylene group, still more preferably an ethylene, trimethylene, or tetramethylene group, and most preferably an ethylene or trimethylene group.

The “C1-C10 alkylene moiety which contains an oxygen atom or a sulfur atom in the carbon chain or at the end of the carbon chain” of the “C1-C10 alkylene group which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain” or the “C1-C10 alkylene group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) which has an oxygen atom or a sulfur atom in said carbon chain or at the end of said carbon chain” in the definition of Z represents a “C1-C10 alkylene group” described above which contains an oxygen atom or a sulfur atom in the carbon chain or at the end of the carbon chain, and can be, for example, a —O—CH2—, —O—(CH2)2—, —O—(CH2)3—, —O—(CH2)4—, —O—(CH2)5—, —O—(CH2)6—, —O—(CH2)7—, —O—(CH2)8—, —O—(CH2)9—, —O—(CH2)10—, —CH2—O—CH2—, —CH2—O—(CH2)2—, —CH2—O—(CH2)3—, —CH2—O—(CH2)4—, —(CH2)2—O—CH2—, —(CH2)2—O—(CH2)2—, —(CH2)2—O—(CH2)3—, —(CH2)2—O—(CH2)4—, —(CH2)3—O—CH2—, —(CH2)3—O—(CH2)2—, —(CH2)3—O—(CH2)3—, —(CH2)4—O—CH2—, —(CH2)4—O—(CH2)2—, —(CH2)5—O—CH2—, —CH2—O—, —(CH2)2—O—, —(CH2) 3—O—, —(CH2)4—O—, —(CH2)5—O—, —(CH2)6—O—, —(CH2)7—O—, —(CH2)8—O—, —(CH2)9—O—, —(CH2)10—O—, —S—CH2—, —S—(CH2)2—, —S—(CH2)3—, —S—(CH2)4—, —S—(CH2)5—, —S—(CH2) 6—, —S—(CH2)7—, —S—(CH2)8—, —S—(CH2)9—, —S—(CH2)10—, —CH2—S—CH2—, —CH2—S—(CH2) 2—, —CH2—S—(CH2)3—, —CH2—S—(CH2)4—, —(CH2)2—S—CH2—, —(CH2)2—S—(CH2)2—, —(CH2)2—S—(CH2)3—, —(CH2)2—S—(CH2)4—, —(CH2)3—S—CH2—, —(CH2)3—S—(CH2)2—, —(CH2)3—S—(CH2)3—, —(CH2)4—S—CH2—, —(CH2)4—S—(CH2)2—, —(CH2)5—S—CH2—, —CH2—S—, —(CH2)2—S—, —(CH2)3—S—, —(CH2)4—S—, —(CH2)5—S—, —(CH2)6—S—, —(CH2)7—S—, —(CH2)8—S—, —(CH2)9—S—, or —(CH2)10—S— group, and is preferably a C1-C6 alkylene group which contains an oxygen atom in the carbon chain or at the end of the carbon chain, more preferably a —O—CH2—, —O—(CH2)2—, —O—(CH2)3—, —CH2—O—, —(CH2)2—O—, or —(CH2)3—O— group, and most preferably a —CH2—O— or —(CH2)2—O—group.

The C3-C10 cycloalkyl moiety of the “C3-C10 cycloalkyl group”, the “C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from Substituent group (a)”, or the “C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b)” in the definition of R5 or Substituent group (b), may optionally be fused with other cyclic groups, and can be, for example, a group such as a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, adamantyl, or indanyl group, and is preferably a C5-C6 cycloalkyl group, and most preferably a cyclohexyl group.

The 5- to 7-membered heterocyclic moiety containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in the “5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom”, the “5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from Substituent group (a)”, or the “5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b) in the definition of R5 or substituent group (b)” can be, forexample, a 5- to 7-membered aromatic heterocyclic or partially or fully hydrogenated saturated heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom.

The heterocyclic group can be a furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperadinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, or pyrazolidinyl group, and is preferably a 5- or 6-membered aromatic heterocyclic group, more preferably a furyl, thienyl, or pyrrolyl group, still more preferably a furyl or thienyl group, and most preferably a thienyl group.

The “aromatic heterocyclic group” described above may optionally be fused with other cyclic groups, and can be, for example, a benzothienyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, carbazolyl, carbolinyl, acridinyl, or isoindolinyl group, and is preferably a benzothienyl group.

The “halogen atom” in the definition of Substituent group (a) can be a fluorine, chlorine, bromine or iodine atom, of which a fluorine or chlorine atom is preferred.

The “lower alkyl group” in the definition of R1, R2, R3, R4,or Substituent group (a) can be, for example, a straight or branched chain alkyl group having from 1 to 6 carbon atoms. Said lower alkyl group can be, for example, a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 1-ethylbutyl or 2-ethylbutyl group, and is preferably a C1-C4 alkyl group, more preferably a C1-C2 alkyl group, and most preferably a methyl group.

The “halogeno lower alkyl group” in the definition of Substituent group (a) is a group wherein said “lower alkyl group” is substituted with a halogen atom. Said halogeno lower alkyl group can be, for example, a halogeno C1-C6 alkyl group such as a trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoromethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl, or 2,2-dibromoethyl group, and is preferably a halogeno C1-C4 alkyl group, more preferably a trifluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, or 2,2,2-trichloroethyl group, and most preferably a trifluoromethyl group.

The “lower alkoxy group” in the definition of Substituent group (a) is a group wherein said “lower alkyl group” is bonded to an oxygen atom. Said lower alkoxy group can be, for example, a straight or branched chain alkoxy group having from 1 to 6 carbon atoms such as a methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, tert-butoxy, pentoxy, isopentoxy, 2-methylbutoxy, 1-ethylpropoxy, 2-ethylpropoxy, neopentoxy, hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, or 2,3-dimethylbutoxy group, and is preferably a C1-C4 alkoxy group, more preferably a C1-C2 alkoxy group, and most preferably a methoxy group.

The “lower alkylthio group” in the definition of Substituent group (a) is a group wherein said “lower alkyl group” is bonded to a sulfur atom. Said lower alkylthio group can be, for example, a straight or branched chain alkylthio group having from 1 to 6 carbon atoms such as a methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, tert-butylthio, pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, hexylthio, 4-methylpentylthio, 3-methylpentylthio, 2-methylpentylthio, 3,3-dimethylbutylthio, 2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, or 2,3-dimethylbutylthio group, and is preferably a C1-C4 alkylthio group, more preferably a C1-C2 alkylthio group, and most preferably a methylthio group.

The “lower alkoxycarbonyl group” in the definition of Substituent group (a) is a group wherein said “lower alkoxy group” is bonded to a carbonyl group. Said lower alkoxycarbonyl group can be, for example, a straight or branched chain alkoxycarbonyl group having from 1 to 6 carbon atoms such as a methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s-butoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl, hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, or 2,3-dimethylbutoxycarbonyl group, and is preferably a C1-C4 alkoxycarbonyl group, more preferably a C1-C2 alkoxycarbonyl group, and most preferably a methoxycarbonyl group.

The “lower aliphatic acyl group” in the definition of Substituent group (a) is a group wherein a hydrogen atom or a saturated or unsaturated aliphatic hydrocarbon group is bonded to a carbonyl group. Said lower aliphatic hydrocarbon group can be, for example, a straight or branched chain lower aliphatic acyl group having from 1 to 8 carbon atoms such as a formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, acryloyl, methacryloyl, or crotonoyl group, and is preferably a C1-C4 lower aliphatic acyl group, more preferably an acetyl or propionyl group, and most preferably an acetyl group.

The “mono lower alkylamino group” in the definition of Substituent group (a) is a group wherein said “lower alkyl group” is bonded to one amino group. Said mono lower alkylamino group can be, for example, a mono-C1-C4 alkylamino group such as a methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, s-butylamino, tert-butylamino, pentylamino, isopentylamino, 2-methylbutylamino, neopentylamino, 1-ethylpropylamino, hexylamino, isohexylamino, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1-methylpentylamino, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino, or 2-ethylbutylamino group, and is preferably a mono-C1-C4 alkylamino group, more preferably a mono-C1-C2 alkylamino group, and most preferably a methylamino group.

The “di-lower alkylamino group” in the definition of Substituent group (a) is a group wherein two said “lower alkyl groups” are bonded to an amino group. Said di-lower alkylamino group can be, for example, a di-C1-C6 alkylamino group such as a dimethylamino, diethylamino, N-ethyl-N-methylamino, dipropylamino, dibutylamino, dipentylamino, or dihexylamino group, and is preferably a di-C1-C4 alkylamino group, more preferably a di-C1-C2 alkylamino group, and most preferably a dimethylamino group.

The “lower aliphatic acylamino group” in the definition of Substituent group (a) is a group wherein said “lower aliphatic acyl group” is bonded to an amino group. Said lower aliphatic acylamino group can be, for example, a straight or branched chain lower aliphatic acylamino group having from 1 to 7 carbon atoms such as a formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, valerylamino, isovalerylamino, pivaloylamino, hexanoylamino, acryloylamino, methacryloylamino, or crotonoylamino group, and is preferably a C1-C4 lower aliphatic acylamino group, more preferably an acetylamino or propionylamino group, and most preferably an acetylamino group.

The “lower alkylsulfonyl group” in the definition of D is a group wherein said “lower alkyl group” is bonded to a sulfonyl group. Said lower alkylsulfonyl group can be, for example, a straight or branched chain alkylsulfonyl group having from 1 to 6 carbon atoms such as a methanesulfonyl, ethanesulfonyl, propanesulfonyl, isopropanesulfonyl, butanesulfonyl, isobutanesulfonyl, s-butanesulfonyl, tert-butanesulfonyl, pentanesulfonyl, isopentanesulfonyl, 2-methylbutanesulfonyl, neopentanesulfonyl, hexanesulfonyl, 4-methylpentanesulfonyl, 3-methylpentanesulfonyl, 2-methylpentanesulfonyl, 3,3-dimethylbutanesulfonyl, 2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl, 1,2-dimethylbutanesulfonyl, 1,3-dimethylbutanesulfonyl, or 2,3-dimethylbutanesulfonyl group, and is preferably a C1-C4 alkylsulfonyl group, more preferably a C1-C2 alkylsulfonyl group, and most preferably a methanesulfonyl group.

The “arylsulfonyl group” in the definition of D is a group wherein said “aryl group” is bonded to a sulfonyl group. Said arylsulfonyl group can be, for example, an arylsulfonyl group having from 6 to 10 carbon atoms such as a benzenesulfonyl, p-toluenesulfonyl, o-xylene-4-sulfonyl, m-xylene-4-sulfonyl, p-xylenesulfonyl, or naphthalenesulfonyl group, and is preferably a benzenesulfonyl group.

The “protecting group of the amino group” in the definitions of R1 and R2 is a protecting group for an amino group which is generally used in the field of synthetic organic chemistry, and can be:

an “aliphatic acyl group”, for example, a “lower aliphatic acyl group” described above, a halogeno lower aliphatic acyl group such as a chloroacetyl, dichloroacetyl, trichloroacetyl, or trifluoroacetyl group, or a lower aliphatic acyl group substituted with a lower alkoxy such as a methoxyacetyl group;

an “aromatic acyl group”, for example, an aromatic acyl group such as a benzoyl, 1-indanecarbonyl, 2-indanecarbonyl, or 1- or 2-naphthoyl group, or an aromatic acyl group substituted with from 1 to 3 substituents selected from Substituent group (a) described above such as a 4-chlorobenzoyl, 4-fluorobenzoyl, 2,4,6-trimethylbenzoyl, 4-toluoyl, 4-anisoyl, 4-nitrobenzoyl, 2-nitrobenzoyl, 2-(methoxycarbonyl)benzoyl, or 4-phenylbenzoyl group;

an “alkoxycarbonyl group”, for example, a “lower alkoxycarbonyl group” described above, or a lower alkoxycarbonyl group substituted with one or more halogen atoms or one or more tri-lower alkylsilyl groups such as a 2,2,2-trichloroethoxycarbonyl or 2-trimethylsilylethoxycarbonyl group;

an “alkenyloxycarbonyl group” such as a vinyloxycarbonyl or allyloxycarbonyl group;

an “aralkyloxycarbonyl group”, for example, an aralkyloxycarbonyl group such as a benzyloxycarbonyl group, or an aralkyloxycarbonyl group substituted with 1 to 3 substituents selected from Substituent group (a) described above such as a 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, or 4-nitrobenzyloxycarbonyl group;

a “silyl group”, for example, a tri-lower alkylsilyl group such as a trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, tert-butyldimethylsilyl, methyldiisopropylsilyl, methyldi(tert-butyl)silyl, or triisopropylsilyl group, or a silyl group substituted with 3 substituents selected from aryl groups or aryl groups and lower alkyl groups such as a diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl, or phenyldiisopropylsilyl group;

an “aralkyl group”, for example, a lower alkyl group substituted with from 1 to 3 aryl groups such as a benzyl, phenethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, or 9-anthrylmethyl group, or a lower alkyl group substituted with from 1 to 3 aryl groups, wherein said aryl group is substituted with a lower alkyl group, a lower alkoxy group, a nitro group, a halogen atom, or a cyano group, such as a 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzyldiphenylmethyl, bis(2-nitrophenyl)methyl, or piperonyl group; or

a “substituted methylene group forming a Schiff base” such as a N,N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, salicylidene, 5-chlorosalicylidene, diphenylmethylene, or (5-chloro-2-hydroxyphenyl) phenylmethylene group.

The “protecting group of the amino group” is preferably a lower aliphatic acyl group, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group, or an aralkyloxycarbonyl group substituted with from 1 to 3 substituents selected from Substituent group (a), particularly preferably an acetyl or tert-butoxycarbonyl group.

The “protecting group of the hydroxyl group” in the definition of R3 represents a “general protecting group in chemical reactions” which can be cleaved by a chemical process such as hydrogenolysis, hydrolysis, electrolysis, and photolysis, or a “protecting group which can be cleaved by a biological process such as hydrolysis in vivo”.

The “general protecting group in chemical reactions” can be, for example,

an “aliphatic acyl group” described above;

an “aromatic acyl group” described above;

a “tetrahydropyranyl or tetrahydrothiopyranyl group” such as a tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, or 4-methoxytetrahydrothiopyran-4-yl group;

a “tetrahydrofuranyl or tetrahydrothiofuranyl group” such as a tetrahydrofuran-2-yl or tetrahydrothiofuran-2-yl group;

a “silyl group” described above;

an “alkoxymethyl group”, for example, a lower alkoxymethyl group such as a methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, or tert-butoxymethyl group, a lower alkoxylated lower alkoxymethyl group such as a 2-methoxyethoxymethyl group, or a halogeno lower alkoxymethyl group such as a 2,2,2-trichloroethoxymethyl or bis(2-chloroethoxy)methyl group;

a “substituted ethyl group”, for example, a lower alkoxylated ethyl group such as a 1-ethoxyethyl or 1-(isopropoxy)ethyl group, or a halogenated ethyl group such as a 2,2,2-trichloroethyl group;

an “aralkyl group” described above;

an “alkoxycarbonyl group” described above;

an “alkenyloxycarbonyl group” described above; or

an “aralkyloxycarbonyl group” described above.

On the other hand, the “protecting group which can be cleaved by a biological process such as hydrolysis in vivo” can be, for example,

a “carbonyloxyalkyl group”, for example,

    • an acyloxyalkyl group such as an ethylcarbonyloxymethyl, pivaloyloxymethyl, dimethylaminoacetoxymethyl, or 1-acetoxyethyl group;
    • a 1-(alkoxycarbonyloxy)alkyl group such a 1-(methoxycarbonyloxy)ethyl, 1-(ethoxycarbonyloxy)ethyl, ethoxycarbonyloxymethyl, 1-(isopropoxycarbonyloxy)ethyl, 1-(tert-butoxycarbonyloxy)ethyl, 1-(ethoxycarbonyloxy)propyl, or 1-(cyclohexyloxycarbonyloxy)ethyl group;
    • a phthalidyl group; or
    • an oxodioxolenylmethyl group such as a 4-methyl-oxodioxolenylmethyl, 4-phenyl-oxodioxolenylmethyl, or oxodioxolenylmethyl group;

an “aliphatic acyl group” described above;

an “aromatic acyl group” described above;

a “residual group of a succinic acid half-ester”;

a “residual group of a phosphoric acid ester”;

a “residual group forming an amino acid ester or the like”;

a carbamoyl group;

a “protecting group of two hydroxyl groups”, for example, an aralkylidene group such as a benzylidene group, an alkoxyethylidene group such as a, methoxyethylidene or ethoxyethylidene group, an oxomethylene group, or a thioxomethylene group; or

a “carbonyloxyalkyloxycarbonyl group” such as a pivaloyloxymethyloxycarbonyl group.

The suitability of such a derivative can be determined by administering it to an experimental animal such as a rat or a mouse by an intravenous injection, measuring a body fluid of the animal thereafter and detecting the original compound or a pharmacologically acceptable salt thereof.

The “protecting group of the hydroxyl group” is preferably a lower aliphatic acyl group, an aromatic acyl group, an aromatic acyl group substituted with from 1 to 3 substituents selected from Substituent group (a), or a silyl group, particularly preferably an acetyl group or a tert-butyldimethylsilyl group.

The “protecting group of phosphoric acid” in the definition of R10 or R11 can be, for example,

    • a lower alkyl group such as a methyl, ethyl, isopropyl, or butyl group,
    • a lower alkyl group substituted with one or more cyano groups such as a 2-cyanoethyl or 2-cyano-1,1-dimethylethyl group,
    • a lower alkyl group substituted with one or more silyl groups wherein said silyl group is substituted with 3 substituents selected from the group consisting of lower alkyl groups or aryl groups and lower alkyl groups such as a 2-(methyldiphenylsilyl)ethyl or 2-trimethylsilylethyl group,
    • a lower alkyl group substituted with one or more heterocyclyl groups such as a 2-(2′-pyridyl)ethyl or 2-(4′-pyridyl)ethyl group,
    • a lower alkyl group substituted with one or more arylthio groups such as a 2-phenylthioethyl, 2-(4′-nitrophenylthio)ethyl, or 2-(4′-triphenylmethylphenylthio)ethyl group,
    • a lower alkyl group substituted with one or more alkylsulfonyl groups, arylsulfonyl groups, or arylalkylsulfonyl groups such as a 2-(tert-butylsulfonyl)ethyl, 2-(phenylsulfonyl)ethyl, or 2-(benzylsulfonyl)ethyl group, or
    • a halogeno lower alkyl group such as a 2,2,2-trichloroethyl, 2,2,2-trichloroethyl-1,1-dimethylethyl, 2,2,2-tribromoethyl, 2,3-dibromopropyl, or 2,2,2-trifluoroethyl group;

an aralkyl group, for example,

    • a lower alkyl group substituted with from 1 to 3 aryl groups, such as a benzyl, phenethyl, 3-phenylpropyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, or 9-anthrylmethyl group,,
    • a lower alkyl group substituted with one or more aryl groups wherein said aryl moiety is substituted with one or more nitro groups, halogen atoms, or lower aliphatic acyl groups, such as an o-nitrobenzyl, 4-nitrobenzyl, 2,4-dinitrobenzyl, 4-chlorobenzyl, 4-chloro-2-nitrobenzyl, or 4-acyloxybenzyl group,
    • a lower alkyl group substituted with one or more aryl groups having one or more substituents such as a 2-nitrophenylethyl group, or
    • a lower alkyl group substituted with one or more fluorenyl groups such as a 9-fluorenylmethyl group;

a lower alkenyl group such as an allyl or propenyl group;

a lower alkenyl group substituted with one or more cyano groups such as a 4-cyano-2-butenyl group;

an aryl group such as a phenyl group;

an aryl group substituted with one or more substituents selected from the group consisting of a lower alkyl group, a lower alkyl group substituted with 3 aryl groups, a lower alkoxy group, a nitro group, and a halogen atom, such as a 2-methylphenyl, 2,6-dimethylphenyl, 2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 2,6-dichlorophenyl, 2-bromophenyl, 4-nitrophenyl, 3,5-dinitrophenyl, 4-chloro-2-nitrophenyl, or 2-methoxy-5-nitrophenyl group; or

an amide such as an anilidate, 4-triphenylmethylanilidate, [N-(2-trityloxy)ethyl]anilidate, p-(N,N-dimethylamino)anilidate, or 3-(N,N-diethylaminomethyl)anilidate.

The “protecting group of phosphoric acid” is preferably a lower alkyl group, a lower alkenyl group, or a methyl group substituted with from 1 to 3 substituents selected from the group consisting of a phenyl group and a naphthyl group, more preferably a methyl group, an ethyl group, an allyl group, or a benzyl group, and most preferably a methyl group or an ethyl group.

The “C3-C10 cycloalkyl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b)” in the definition of R5 can be, for example, a 2-fluorocyclopropyl, 2-chlorocyclopropyl, 2- or 3-fluorocyclopentyl, 2- or 3-chlorocyclopentyl, 2-, 3- or 4-fluorocyclohexyl, 2-, 3- or 4-chlorocyclohexyl, 2-, 3- or 4-bromocyclohexyl, 2-, 3- or 4-iodocyclohexyl, 2-methylcyclopropyl, 2-ethylcyclopropyl, 2- or 3-methylcyclopentyl, 2- or 3-ethylcyclopentyl, 2-, 3- or 4-methylcyclohexyl, 2-, 3- or 4-ethylcyclohexyl, 2-trifluoromethylcyclopropyl, 2- or 3-trifluoromethylcyclobutyl, 2- or 3-trifluoromethylcyclopentyl, 2-, 3- or 4-trifluoromethylcyclohexyl, 2-methoxycyclopropyl, 2- or 3-methoxycyclobutyl, 2- or 3-methoxycyclopentyl, 2-, 3- or 4-methoxycyclohexyl, 2-, 3- or 4-ethoxycyclohexyl, 2-, 3- or 4-propoxycyclohexyl, 2-, 3- or 4-isopropoxycyclohexyl, 2-, 3- or 4-(1-ethylpropoxy)cyclohexyl, 2-, 3- or 4-(2-ethylpropoxy)cyclohexyl, 2-carboxycyclopropyl, 2- or 3-carboxycyclopentyl, 2-, 3- or 4-carboxycyclohexyl, 2-methoxycarbonylcyclopropyl, 2- or 3-methoxycarbonylcyclopentyl, 2-, 3- or 4-methoxycarbonylcyclohexyl, 2-hydroxycyclopropyl, 2- or 3-hydroxycyclopentyl, 2-, 3- or 4-hydroxycyclohexyl, 2-formylcyclopropyl, 2- or 3-formylcyclopentyl, 2-, 3- or 4-formylcyclohexyl, 2-acetylcyclopropyl, 2- or 3-acetylcyclopentyl, 2-, 3- or 4-acetylcyclohexyl, 2-aminocyclopropyl, 2- or 3-aminocyclopentyl, 2-, 3- or 4-aminocyclohexyl, 2-methylaminocyclopropyl, 2- or 3-methylaminocyclobutyl, 2- or 3-methylaminocyclopentyl, 2-, 3- or 4-methylaminocyclohexyl, 2-dimethylaminocyclopropyl, 2- or 3-dimethylaminocyclobutyl, 2- or 3-dimethylaminocyclopentyl, 2-, 3- or 4-dimethylaminocyclohexyl, 2-cyanocyclopropyl, 2- or 3-cyanocyclopentyl, 2-, 3- or 4-cyanocyclohexyl, 2- or 3-cyclohexylcyclopentyl, 2-, 3- or 4-cyclohexylcyclohexyl, 2-phenylcyclopropyl, 2- or 3-phenylcyclopentyl, 2-, 3- or 4-phenylcyclohexyl, 3,4-difluorocyclohexyl, 3,4-dichlorocyclohexyl, 2,3-dimethoxycyclohexyl, 3,4-dimethoxycyclohexyl, 3,5-dimethoxycyclohexyl, or 3,4,5-trimethoxycyclohexyl group, and is preferably a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents (said substituent(s) being selected from the group consistingof halogen atoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxy groups, lower alkylthio groups, and lower aliphatic acyl groups), more preferably a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents (said substituent(s) being selected from the group consisting of halogen atoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxy groups, and lower aliphatic acyl groups), still more preferably a C3-C10 cycloalkyl group substituted with from 1 to 3 substituents (said substituent(s) being selected from the group consisting of halogen atoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxy groups, and lower aliphatic acyl groups), and most preferably a cyclohexyl group substituted with one substituent (said substituent is selected from the group consisting of a fluorine atom, a chlorine atom, methyl, trifluoromethyl, methoxy and acetyl groups).

The “C6-C10 aryl group substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b)” in the definition of R5 can be, for example, a 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-chlorophenyl, 2-, 3- or 4-bromophenyl, 2-, 3- or 4-iodophenyl, 2-, 3- or 4-methylphenyl, 2-, 3- or 4-ethylphenyl, 2-, 3- or 4-propylphenyl, 2-, 3- or 4-butylphenyl, 2-, 3- or 4-pentylphenyl, 2-, 3- or 4-trifluoromethylphenyl, 2-, 3- or 4-methoxyphenyl, 2-, 3- or 4-ethoxyphenyl, 2-, 3- or 4-propoxyphenyl, 2-, 3- or 4-isopropoxyphenyl, 2-, 3- or 4-butoxyphenyl, 2-, 3- or 4-(1-ethylpropoxy)phenyl, 2-, 3- or 4-(2-ethylpropoxy)phenyl, 2-, 3-or 4-methylthiophenyl, 2-, 3- or 4-ethylthiophenyl, 2-, 3- or 4-carboxyphenyl, 2-, 3- or 4-methoxycarbonylphenyl, 2-, 3- or 4-ethoxycarbonylphenyl, 2-, 3- or 4-hydroxyphenyl, 2-, 3- or 4-formylphenyl, 2-, 3- or 4-acetylphenyl, 2-, 3- or 4-aminophenyl, 2-, 3- or 4-methylaminophenyl, 2-, 3- or 4-dimethylaminophenyl, 2-, 3- or 4-cyanophenyl, 2-, 3- or 4-cyclopentylphenyl, 2-, 3- or 4-cyclohexylphenyl, 2-, 3- or 4-biphenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3,4-dibromophenyl, 2,3-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3-fluoro-4-methoxyphenyl, 4-methyl-2-methoxyphenyl, 6-fluoro-4-methyl-2-methoxyphenyl, 5-fluoroinden-3-yl, 5-methylinden-3-yl, 5-methoxyinden-3-yl, 5-fluoroinden-2-yl, 5-chloroinden-2-yl, 5-methylinden-2-yl, 5-methoxyinden-2-yl, 5-hydroxyinden-3-yl, 5-nitroinden-3-yl, 5-cyclohexylinden-3-yl, 5-phenylinden-3-yl, 5-phenoxyinden-3-yl, 5-benzyloxyinden-3-yl, 5-phenylthioinden-3-yl, 5-hydroxyinden-2-yl, 5-nitroinden-2-yl, 5-cyclohexylinden-2-yl, 5-phenylinden-2-yl, 5-fluoronaphthalen-2-yl, 5-methylnaphthalen-2-yl, 5-methoxynaphthalen-2-yl, 5-fluoronaphthalen-1-yl, 5-methylnaphthalen-1-yl, 5-methoxynaphthalen-1-yl, 5-hydroxynaphthalen-2-yl, 5-nitronaphthalen-2-yl, 5-cyclohexylnaphthalen-2-yl, 5-phenylnaphthalen-2-yl, 5-phenoxynaphthalen-2-yl, 5-benzyloxynaphthalen-2-yl, 5-phenylthionaphthalen-2-yl, 5-hydroxynaphthalen-1-yl, 5-nitronaphthalen-1-yl, 5-cyclohexylnaphthalen-1-yl, or 5-phenylnaphthalen-1-yl group, and is preferably a C6-C10 aryl group substituted with from 1 to 3 substituents (said substituent(s) being selected from the group consisting of halogen atoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxy groups, a lower alkylthio groups, and lower aliphatic acyl groups), more preferably a C6-C10 aryl group substituted with from 1 to 3 substituents (said substituent(s) being selected from the group consisting of halogen atoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxy groups, and lower aliphatic acyl groups), still more preferably a phenyl group substituted with from 1 to 3 substituents (said substituent(s) being selected from the group consisting of halogen atoms, lower alkyl groups, halogeno lower alkyl groups, lower alkoxy groups, and lower aliphatic acyl groups), particularly preferably a phenyl group substituted with 1 or 2 substituents (said substituent(s) being selected from the group consisting of fluorine atoms, chlorine atoms, methyl, trifluoromethyl, methoxy and acetyl groups; but, in the case of methoxy group, a phenyl groupsubstituted with from 1 to 3 methoxy groups is preferred), and most preferably a 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,4-ditrifluoromethylphenyl, 3,5-ditrifluoromethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3-acetylphenyl, or 4-acetylphenyl group.

The “5- to 7-membered heterocyclic group containing from 1 to 3 heteroatoms selected from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom in which said heterocyclic group is substituted with from 1 to 3 substituents selected from the group consisting of Substituent group (a) and Substituent group (b)” in the definition of R5 can be, for example, a 3-, 4- or 5-methylfuran-2-yl, 2-, 4- or 5-methylfuran-3-yl, 3-, 4- or 5-fluorothiophen-2-yl, 2-, 4- or 5-fluorofuran-3-yl, 3-, 4- or 5-bromothiophen-2-yl, 2-, 4- or 5-bromofuran-3-yl, 3-, 4- or 5-methylthiophen-2-yl, 2-, 4- or 5-methylthiophen-3-yl, 3-, 4- or 5-ethylthiophen-2-yl, 2-, 4- or 5-ethylthiophen-3-yl, 3-, 4- or 5-methoxythiophen-2-yl, 2-, 4- or 5-methoxythiophen-3-yl, 3- or 4-methylthiazol-5-yl, 3-, 4- or 5-fluorobenzothiophen-2-yl, 3-, 4- or 5-bromobenzothiophen-2-yl, 3-, 4- or 5-methylbenzothiophen-2-yl, 3-, 4- or 5-methoxybenzothiophen-2-yl, 2-, 4- or 5-fluorobenzothiophen-3-yl,2-, 4- or 5-bromobenzothiophen-3-yl, 2-, 4- or 5-methylbenzothiophen-3-yl, 2-, 4- or 5-methoxybenzothiophen-3-yl, 4-, 5-, 6- or 7-methylbenzothiophen-2-yl, 3-, 4- or 5-hydroxyfuran-2-yl, 2-, 4- or 5-hydroxyfuran-3-yl, 3-, 4- or 5-hydroxythiophen-2-yl, 3-, 4- or 5-nitrothiophen-2-yl, 3-, 4- or 5-phenylthiophen-2-yl, 2-, 4- or 5-hydroxythiophen-3-yl, 2-, 4- or 5-cyanothiophen-3-yl, 1-, 2- or 3-hydroxypyridin-4-yl, 1-, 2- or 3-cyanopyridin-4-yl, or 1-, 2- or 3-phenylpyridin-4-yl group, and is preferably a 3-, 4- or 5-fluorothiophen-2-yl or 2-, 4- or 5-fluorofuran-3-yl group.

The “pharmacologically acceptable salt thereof” means a salt which, when the compounds of general formula (I), (II), or (III) of the present invention have a basic group such as an amino group, can be prepared by reacting the compounds with an acid, and when the compounds of general formula (I), (II), or (III) of the present invention have an acidic group such as a carboxyl group or a phosphate group, can be prepared by reacting the compounds with a base. Such salts are included in the present invention.

The salt, when the compounds of general formula (I), (II), or (III) have a basic group, can be an inorganic acid salt, for example, a hydrohalide such as hydrofluoride, hydrochloride, hydrobromide, or hydroiodide, a nitrate, a perchlorate, a sulfate, a phosphate or the like; an organic acid salt, for example, a lower alkanesulfonate such as methanesulfonate, trifluoromethanesulfonate, or ethanesulfonate, an arylsulfonate such as benzenesulfonate or p-toluenesulfonate, an acetate, a malate, a fumarate, a succinate, a citrate, an ascorbate, a tartrate, an oxalate, a maleate, or the like; or an amino acid salt such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamic acid salt, or aspartic acid salt. The salt is preferably an organic acid salt (particularly fumarate, oxalate or maleate) or a hydrohalide (particularly hydrochloride).

The salt, when the compounds of general formula (I), (II), or (III) have an acidic group, can be a metal salt, for example, an alkali metal salt such as sodium salt, potassium salt, or lithium salt, an alkaline earth metal salt such as calcium salt or magnesium salt, an aluminum salt, an iron salt, or the like; an amine salt, for example, an inorganic amine salt such as ammonium salt, an organic amine salt such as t-octylamine salt, dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzylphenethylamine salt, piperazine salt, tetramethylammonium salt, tris(hydroxymethyl)aminomethane salt, or the like; or an amino acid salt such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamic acid salt, or aspartic acid salt. The salt preferably is an alkali metal salt (particularly sodium salt).

When the compounds of general formula (I), (II), or (III), pharmacologically acceptable salts thereof, or pharmacologically acceptable esters thereof of the present invention are allowed to stand in contact with the atmosphere or to recrystallize, they may absorb water or water may attach to them to form a hydrate. The present invention encompasses such hydrates.

The compounds of general formula (I), (II), or (III), pharmacologically acceptable salts, or pharmacologically .acceptable esters thereof of the present invention have one or more asymmetric carbon atoms in their structures, and can exist as optical isomers due to such asymmetric carbon atoms. In the present invention, a single optical isomer and mixtures of optical isomers are represented as a single chemical formula (I), (II), or (III) individually. The present invention encompasses both individual optical isomers and mixtures thereof in any ratio.

In the compounds as shown in formulas (I), (II) and (III), preferred compounds are compounds in which the asymmetric carbon to which the formula —NR1R2 attaches, is the R configuration.

The “ester thereof” described above indicates an ester of compounds of general formula (I), (II), or (III) of the present invention which have a group capable of being esterified. The ester can be an “ester of a hydroxyl group” or an “ester of a carboxyl group”. Each ester residual group belongs to a “general protecting group in chemical reactions” or a “protecting group which can be cleaved by a biological process such as hydrolysis in vivo”.

The “general protecting group in chemical reactions” is a protecting group which can be cleaved by a chemical process such as hydrogenolysis, hydrolysis, electrolysis, and photolysis.

The “general protecting group in chemical reactions” and the “protecting group which can be cleaved by a biological process such as hydrolysis in vivo” related to the “ester of a hydroxyl group” have the same meanings as those described above for the “protecting group of the hydroxyl group”.

The “general protecting group in chemical reactions” related to the “ester of a carboxyl group” is preferably a “lower alkyl group” described above; a lower alkenyl group such as ethenyl, 1-propenyl, 2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, or 5-hexenyl; a lower alkynyl group such as ethynyl, 2-propynyl, 1-methyl-2-propynyl, 2-butynyl, 1-methyl-2-butynyl, 1-ethyl-2-butynyl, 3-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butynyl, 2-pentynyl, 1-methyl-2-pentynyl, 3-pentynyl, 1-methyl-3-pentynyl, 2-methyl-3-pentynyl, 4-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl; a “halogeno lower alkyl group” described above; a hydroxy “lower alkyl group” such as 2-hydroxyethyl, 2,3-dihydroxypropyl, 3-hydroxypropyl, 3,4-dihydroxybutyl, or 4-hydroxybutyl; a “lower aliphatic acyl”-“lower alkyl group” such as acetylmethyl; an “aralkyl group” described above; or a “silyl group” described above.

The “protecting group which can be cleaved by a biological process such as hydrolysis in vivo” related to the “ester of a carboxyl group” is preferably an “alkoxyalkyl group” such as a lower alkoxy lower alkyl group, e.g., methoxyethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, 1-(isopropoxy)ethyl, 2-methoxyethyl, 2-ethoxyethyl, ethoxymethyl, n-propoxymethyl, isopropoxymethyl, n-butoxymethyl, or t-butoxymethyl, a lower alkoxylated lower alkoxy lower alkyl group, e.g., 2-methoxyethoxymethyl, an “aryl”oxy “lower alkyl group”, e.g., phenoxymethyl, or a halogenated lower alkoxy lower alkyl group, e.g., 2,2,2-trichloroethoxymethyl or bis(2-chloroethoxy)methyl; a “lower alkoxy”carbonyl“lower alkyl group” such as methoxycarbonylmethyl; a cyano “lower alkyl group” such as cyanomethyl or 2-cyanoethyl; a “lower alkyl” thiomethyl group such as methylthiomethyl or ethylthiomethyl; an “aryl” thiomethyl group such as phenylthiomethyl or naphthylthiomethyl; a “lower alkyl” sulfonyl “lower alkyl group” which may be substituted with one or more halogen atoms such as 2-methanesulfonylethyl or 2-trifluoromethanesulfonylethyl; an “aryl” sulfonyl “lower alkyl group” such as 2-benzenesulfonylethyl or 2-toluenesulfonylethyl; a 1-(acyloxy) “lower alkyl group” described above; a “phthalidyl group” described above; an “aryl group” described above; a “lower alkyl group” described above; a “carboxyalkyl group” such as carboxymethyl; or an “amide forming residual group of an amino acid” such as phenylalanine.

The more preferred “general protecting group in chemical reactions” and “protecting group which can be cleaved by a biological process such as hydrolysis in vivo” related to the “ester of a carboxyl group” described above is a lower alkyl or aralkyl group.

“Immunosuppressants”, which are an active ingredient of pharmaceutical compositions of the present invention, are agents preventing or inhibiting the progression of immune responses as well as compounds with immunosuppressive activity, and are classified into the following groups on the basis of mechanism of action:

(1) agents which have the action of inhibiting intracellular signal transduction involved in cytokine expression of T-cells, include those blocking cytokine production as well as those preventing cytokine signaling from acting on immune cells by inhibiting the intracellular signal transduction. Such agents, which have the action of inhibiting the intracellular signal transduction involved in cytokine expression of T-cells, include, for example,

S7481/F-1 or a pharmacologically acceptable salt thereof disclosed in the specification of U.S. Pat. No. 4,117,118 [preferably cyclosporin A, of which the chemical name is cyclo[3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-2-aminobutyryl-methylglycyl-methyl-leucyl-valyl-methyl-leucyl-alanyl-alanyl-methyl-leucyl-methyl-leucyl-methyl-valyl.],

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 184,162 {preferably tacrolimus, of which the chemical name is 17-allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone.},

rapamycin disclosed in the specification of U.S. Pat. No. 3,929,992 [of which the chemical name is 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone.],

a compound having the general formula (II) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 94,632 (Japanese Patent Publication (Kokai) Number Sho 58-62152) [preferably gusperimus, of which the chemical name is N-[4-(3-aminopropyl)aminobutyl]carbamoylhydroxymethyl-7-guanidinoheptanamide, and in the present invention gusperimus includes a pharmacologically acceptable salt (trihydrochloride) thereof.],

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of U.S. Pat. No. 5,912,253 {preferably everolimus, of which the chemical name is 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[2-[4-hydroxyethoxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]azacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone.},

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 600,762 {preferably tresperimus, of which the chemical name is 2-[4-(3-aminopropylamino)butyl]aminocarbonyloxy-N-[6-(aminoiminomethyl)aminohexyl]acetamide, and in the present invention tresperimus includes a pharmacologically acceptable salt thereof.},

LF15-0195 disclosed in Int. J. Immunopharmacol., vol. 21 (5), 349-358 (1999) {anisperimus, of which the chemical name is [(6-guanidinohexyl)carbamoyl]methyl[4-(3-aminobutyl)aminobutyl]carbamate.},

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 626,385 (Japanese Patent Number 3076724 or U.S. Pat. No. 5,493,019) {preferably SDZ-281-240, of which the chemical name is 17-ethyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone, and in the present invention SDZ-281-240 includes a pharmacologically acceptable salt thereof.},

a compound having the general formula (VII) or a pharmacologically acceptable salt thereof disclosed in the specification of WO Publication Number 93/04680 (E.P. Publication Number 642,516) {preferably ABT-281, of which the chemical name is 17-ethyl-1,14-dihydroxy-12-[2-(4-tetrazolyl-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone.},

a compound having the general formula (A) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 414,632 {preferably tigderimus, of which the chemical name is cyclo[[3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-[3-O-(2-hydroxyethyl)-D-seryl]-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl.],

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of WO Publication Number 97/11080.{preferably A-119435, of which the chemical name is 17-ethyl-1,14-dihydroxy-12-[2-[4-(acetylaminoacetylthio)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone.}, and 17-ethyl-1,14-dihydroxy-12-[2-[4-(2-phenylhydrazinocarbonyloxy)-3-methoxycyclohexyl]-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone disclosed in Bioorg. Med. Chem. Lett., vol. 9 (2), 227-232 (1999).

The planar chemical structures of the typical compounds are shown below.

(2) Agents which have the action of inhibiting nucleoside synthesis in immune cells, depress lymphocytic proliferation by inhibiting nucleoside synthesis in the immune cells andshow nonspecific immunosuppressive activity. Such agents,which have the action of inhibiting nucleoside synthesis in the immune cells, include, for example,

a compound having the chemical structure disclosed in claim 1 of U.S. Pat. No. 3,888,843 (mizoribine, of which the chemical name is 5-hydroxy-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide),

a compound having the general formula disclosed in claim 7 of U.S. Pat. No. 3,056,785 or a pharmacologically acceptable salt thereof [preferably azathioprine, of which the chemical name is 6-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine, and in the present invention azathioprine includes a pharmacologically acceptable salt (hydrochloride) thereof],

a compound having the general formula (A) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 281,713 (U.S. Pat. No. 4,753,935) [preferably mycophenolate Mofetil, of which the chemical name is 2-(4-morpholinyl)ethyl-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-(4E)-hexenoate.],

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 13376 (Japanese Patent Publication (Kokai) Number Sho 62-72614 or U.S. Pat. No. 4,284,786) [preferably leflunomide, of which the chemical name is 5-methyl-N-[4-(trifluoromethyl)phenyl]-4-isoxazolecarboxamide.],

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of WO Publication Number 97/40028 {preferably merimempodib, of which the chemical name is (3s)-tetrahydro-3-furanyl [[3-[[[[3-methoxy-4-(5-oxazolyl)phenyl]amino]carbonyl]amino]phenyl]methyl]carbamate.},

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of FR Patent Publication Number 2,727,628 [preferably HMR-1279, of which the chemical name is α-cyano-N-(4-cyanophenyl)-β-oxo-cyclopropanepropaneamide.],

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in thespecification of WO Publication Number 93/22286 (Japanese Patent Number 2,928,385, E.P. Publication Number 601,191 or U.S. Pat. No. 5,371,225) {preferably TSK-204, of which the chemical name is 6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H-benzo[6,7]cyclohepta[1,2-b]quinoline-8-carboxylic acid.}, and

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of E.P. Publication Number 569,912 (Japanese Patent Publication (Kokai) Number Hei 6-32784) {preferably SP-100030, of which the chemical name is 2-chloro-N-[3,5-di(trifluoromethyl)phenyl]-4-(trifluoromethyl)pyrimidine-5-carboxyamide.}.

The planar chemical structures of the typical compounds are shown below.

(3) Agents which inhibit the action of cytokines on immune cells and have antirheumatic action, have the combination of suppression of cytokine production, suppression of lymphocytic proliferation, and suppression of immunoglobulin production. Furthermore, the agents include compounds having suppressive action on T-cell proliferation, suppression of NK cell activity, TNF-receptor antagonistic action, and the like. Such agents, which inhibit the action of cytokine on immune cells and have antirheumatic action, include, for example,

a compound having the general formula disclosed in claim (1) of Japanese Patent Publication (Kokai) Number Hei 2-49778 or a pharmacologically acceptable salt thereof (preferably T-614, of which the chemical name is N-[3-formylamino-4-oxo-6-phenoxy-4H-1-benzopyran-7-yl]methanesulfonamide.),

a compound having the general formula (I) disclosed in the specification of U.S. Pat. No. 4,720,506 or a pharmacologically acceptable salt thereof [preferably actarit, of which the chemical name is 4-(acetylamino)phenylacetic acid.],

a compound having the general formula disclosed in claim 1 of U.S. Patent Number 2,396,145 or a pharmacologically acceptable salt thereof {preferably salazosulfapyridine, of which the chemical name is 5-[[p-(2-pyridylsulfamoyl)-phenyl]azo]salicylic acid.}, and

a compound having the general formula (I) disclosed in the specification of WO Publication Number 97/23457 {preferably CDC-801, of which the chemical name is 3-phthalimido-3-(3-cyclopentyloxy-4-methoxyphenyl)propionamide.}.

The planar chemical structures of the typical compounds are shown below.

(4) Agents which are alkylating agents causing cell death by breakdown of DNA chains or blocking DNA synthesis, include, for example,

a compound having the general formula (IIIa) or a pharmacologically acceptable salt thereof disclosed in thespecification of U.S. Pat. No. 3,018,302 [preferably cyclophosphamide, of which the chemical name is N,N′-bis-(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide.].

(5) Metabolic antagonists, which inhibit the metabolism of nucleic acids by blocking folic acid production, have the action of inhibiting the metabolism of nucleic acids bybinding to dihydrofolate reductases and blocking theproduction of tetrahydrofolic acids that are essential to the synthesis of components of nucleic acids. Such metabolic antagonists, which inhibit the metabolism of nucleic acids by blocking folic acid production, include, for example,

a compound having the general formula disclosed in claim 1 of U.S. Pat. No. 2,512,572 or a pharmacologically acceptable salt thereof {preferably methotrexate, of which the chemical name is N-[4-[[2,4-diamino-6-pteridinyl]methyl]methylamino]benzoyl-L-glutamic acid.}.

(6) The group of protein drugs, which have the suppression action of TNF-alpha, includes compounds such as IL-1 receptor antagonists, soluble IL-1 receptors, and anti-IL-6 receptor antibodies, which suppress the action of TNF-alpha by inhibiting the neutralizing action of circulating TNF-alpha and its receptor-mediated intracellular TNF-alpha signaling. Such protein drugs, which have the inhibitory action of TNF-alpha, include, for example,

remicade (infliximab) disclosed in the specification of U.S. Pat. No. 5,656,272 and Drugs, vol. 59(6), 1341-1359 (2000),

enbrel (etanercept) disclosed in the specification of WO Publication Number 94/06,476, U.S. Pat. No. 5,605,690, and Expert. Opin. Pharmacother., July vol. 2(7), 1137-1148 (2000),

daclizumab disclosed in the specification of WO Publication Number 92/11,018, U.S. Pat. No. 5,530,101, and N. Engl. J. Med., vol. 338(3), 161-165 (1997),

basiliximab disclosed in the specification of E.P. Publication Number 449,769 and Clin. Pharmacol. Ther., Vol. 64(1), 66-72 (1998),

alemtuzumab disclosed in the specification of WO Publication Number 89/07,452, U.S. Pat. No. 5,846,534, and J. Clin. Oncol., vol. 15(4), 1567-1574 (1997),

omalizumab disclosed in the specification of U.S. Pat. No. 5,965,709 and Drugs vol. 61(2), 253-260 (2001),

BMS-188667 disclosed in the specification of E.P. Publication Number 613,944 and J. Pharm. Sci., vol. 84(12), 1488-1489 (1995),

CDP-571 disclosed in Arthritis-Rheum., vol. 37(9), Suppl., S295 (1994),

inolimomab and ATM-027 disclosed in Transplant., June, vol. 55, 1320-1327 (1993), and

BTI-322 disclosed in Blood, Dec 1, vol. 92(11), 4066-4071 (1998).

(7) Agents which are steroid hormone agents that bind to intracellular steroid receptors to form a complex which binds to reaction sites on chromosomes, resulting in the synthesis of proteins which show immunosuppressive activity, include, for example, prednisolone (of which the chemical name is 1,4-pregnadiene-3,20-dione-11β,17α-21-triol.).

(8) Agents which are substances suppressing prostaglandin production and/or nonsteroidal anti-inflammatory drugs antagonizing the action of prostaglandin, include, for example,

a compound having the general formula disclosed in claim 1 of Japanese Patent Publication (Kokoku) Number Sho 58-4699 or a pharmacologically acceptable salt thereof {preferably loxoprofen sodium, of which the chemical name is sodium 2-[4-(2-oxocyclopentan-1-ylmethyl)phenyl]propionate.},

a compound having the general formula I(A) or a pharmacologically acceptable salt thereof disclosed in thespecification of U.S. Pat. No. 3,558,690 {preferably diclofenac sodium, of which the chemical name is sodium [o-(2,6-dichloroanilino)phenyl]acetate.},

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in thespecification of U.S. Pat. No. 4,233,299 (E.P. Publication Number 0,002,482 or Japanese Patent Publication (Kokai) Number Sho 58-92976) [preferably meloxicam, of which the chemical name is 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide.],

a compound having the general formula (II) or a pharmacologically acceptable salt thereof disclosed in the specification of WO Publication Number 95/15316 (U.S. Pat. No. 5,521,207 or Japanese Patent Publication (Kokai) Number 2000-109466) {preferably celecoxib, of which the chemical name is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide.}, and

a compound having the general formula (I) or a pharmacologically acceptable salt thereof disclosed in the specification of WO Publication Number 95/00501 (U.S. Pat. No. 5,474,995) {preferably rofecoxib, of which the chemical name is 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone.}.

Of the above immunosuppressants, more preferred are cyclosporin A, tacrolimus, rapamycin, leflunomide, methotrexate, remicade and enbrel.

The “pharmacologically acceptable salt thereof” described above means a salt into which the above immunosuppressants can be converted, by reacting a compound having a basic group such as an amino group with an acid or by reacting a compound having an acidic group such as a carboxyl group with a base. Such salts are included in the present invention.

The salt formed with a basic group of the above immunosuppressants is preferably an inorganic acid salt, for example, a hydrohalide such as hydrofluoride, hydrochloride, hydrobromide, or hydroiodide, a nitrate, a perchlorate, a sulfate, a phosphate or the like; an organic acid salt, for example, a lower alkanesulfonate such as methanesulfonate, trifluoromethanesulfonate, or ethanesulfonate, an arylsulfonate such as benzenesulfonate or p-toluenesulfonate, an acetate, a malate, a fumarate, a succinate, a citrate, an ascorbate, a tartrate, a oxalate, a maleate, or the like; or an amino acid salt such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate, or aspartic acid salt. The salt is more preferably hydrochloride, acetate, fumarate, succinate, or maleate.

The salt formed with an acidic group of the above immunosuppressants is preferably a metal salt, for example, an alkali metal salt such as sodium salt, potassium salt, or lithium salt, an alkaline earth metal salt such as calcium salt or magnesium salt, an aluminum salt, an iron salt, or the like; an amine salt, for example, an inorganic salt such as ammonium salt, an organic acid salt such as t-octylamine salt, dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzylphenethylamine salt, piperazine salt, tetramethylammonium salt, tris(hydroxymethyl)aminomethane salt, or the like; or an amino acid salt such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamic acid salt, or aspartic acid salt. The salt is more preferably sodium salt, potassium-salt, calcium salt, magnesium salt, or aluminum salt.

When the immunosuppressants, the active ingredients of the pharmaceutical compositions of the present invention, are allowed to stand in contact with the atmosphere or to recrystallize, they may absorb water or water may attach to them to form a hydrate. The present invention encompasses such hydrates.

When the immunosuppressants, the active ingredients of the pharmaceutical compositions of the present invention, have asymmetric carbons in their structures, these compounds can exist as various stereoisomers due to such asymmetric carbons. In the present invention these compounds are represented as a single chemical formula individually. The present invention encompasses both individual stereoisomers and mixtures of two or more stereoisomers in any ratio.

Compounds shown in the following Table 1, Table 2, Table 3, Table 4, Table 5 and Table 6 are specifically illustrated as preferred compounds of general formula (I), (II), or (III) of the present invention. However, the compounds of the present invention are not limited to these.

The compounds represented by the same compound number in Table 1 and Table 2 include compounds wherein X is a sulfur atom (S), an oxygen atom (O), or a group of formula ═N—CH3.

The compounds represented by the same compound number in Table 5 and Table 6 include the six types of compounds wherein X is a sulfur atom (S), an oxygen atom (O), or a group of formula ═N—CH3, and the phosphate group is linked to an oxygen atom (O) or a —CH2— group.

The meaning of the abbreviations in the following Tables is shown below.

  • Bu represents a butyl group,
  • iBu represents a isobutyl group,
  • Bz represents a benzyl group,
  • Et represents an ethyl group,
  • cHx represents a cyclohexyl group,
  • Me represents a methyl group,
  • Np(1) represents a naphthalen-1-yl group,
  • Np(2) represents a naphthalen-2-yl group,
  • Ph represents a phenyl group,
  • cPn represents a cyclopentyl group,
  • Pr represents a propyl group, and

iPr represents an isopropyl-group.

TABLE 1
Compd. R1 R2 R3 R4 n —Y—Z—R5 R6 R7
1-1 H H H Me 2 —(CH2)3-cHx H H
1-2 H H H Me 2 —(CH2)3-(4-F-cHx) H H
1-3 H H H Me 2 —(CH2)3-(4-Me-cHx) H H
1-4 H H H Me 2 —(CH2)3-(4-Et-cHx) H H
1-5 H H H Me 2 —(CH2)3-(4-CF3-cHx) H H
1-6 H H H Me 2 —(CH2)3-(4-MeO-cHx) H H
1-7 H H H Me 2 —(CH2)3-(4-EtO-cHx) H H
1-8 H H H Me 2 —(CH2)3-(4-MeS-cHx) H H
1-9 H H H Me 2 —(CH2)3-(4-cHx-cHx) H H
1-10 H H H Me 2 —(CH2)3-(4-Ph-cHx) H H
1-11 H H H Me 2 —(CH2)3—Ph H H
1-12 H H H Me 2 —(CH2)3-(4-F—Ph) H H
1-13 H H H Me 2 —(CH2)3-(4-Me—Ph) H H
1-14 H H H Me 2 —(CH2)3-(4-Et—Ph) H H
1-15 H H H Me 2 —(CH2)3-(4-CF3—Ph) H H
1-16 H H H Me 2 —(CH2)3-(4-MeO—Ph) H H
1-17 H H H Me 2 —(CH2)3-(4-EtO—Ph) H H
1-18 H H H Me 2 —(CH2)3-(4-MeS—Ph) H H
1-19 H H H Me 2 —(CH2)3-(4-cHx-Ph) H H
1-20 H H H Me 2 —(CH2)3-(4-Ph—Ph) H H
1-21 H H H Me 2 —(CH2)4-cHx H H
1-22 H H H Me 2 —(CH2)4-(4-F-cHx) H H
1-23 H H H Me 2 —(CH2)4-(4-Me-cHx) H H
1-24 H H H Me 2 —(CH2)4-(4-Et-cHx) H H
1-25 H H H Me 2 —(CH2)4-(4-CF3-cHx) H H
1-26 H H H Me 2 —(CH2)4-(4-MeO-cHx) H H
1-27 H H H Me 2 —(CH2)4-(4-EtO-cHx) H H
1-28 H H H Me 2 —(CH2)4-(4-MeS-cHx) H H
1-29 H H H Me 2 —(CH2)4-(4-cHx-cHx) H H
1-30 H H H Me 2 —(CH2)4-(4-Ph-cHx) H H
1-31 H H H Me 2 —(CH2)4—Ph H H
1-32 H H H Me 2 —(CH2)4-(4-F—Ph) H H
1-33 H H H Me 2 —(CH2)4-(4-Me—Ph) H H
1-34 H H H Me 2 —(CH2)4-(4-Et—Ph) H H
1-35 H H H Me 2 —(CH2)4-(4-CF3—Ph) H H
1-36 H H H Me 2 —(CH2)4-(4-MeO—Ph) H H
1-37 H H H Me 2 —(CH2)4-(4-EtO—Ph) H H
1-38 H H H Me 2 —(CH2)4-(4-MeS—Ph) H H
1-39 H H H Me 2 —(CH2)4-(4-cHx-Ph) H H
1-40 H H H Me 2 —(CH2)4-(4-Ph—Ph) H H
1-41 H H H Me 2 —(CH2)5-cPn H H
1-42 H H H Me 2 —(CH2)5-cHx H H
1-43 H H H Me 2 —(CH2)5-cHx Me H
1-44 H H H Me 2 —(CH2)5-cHx H Me
1-45 H H H Me 2 —(CH2)5-cHx F H
1-46 H H H Me 2 —(CH2)5-cHx H F
1-47 H H H Me 2 —(CH2)5-(3-F-cHx) H H
1-48 H H H Me 2 —(CH2)5-(4-F-cHx) H H
1-49 H H H Me 2 —(CH2)5-(4-Cl-cHx) H H
1-50 H H H Me 2 —(CH2)5-(4-Br-cHx) H H
1-51 H H H Me 2 —(CH2)5-(3-Me-cHx) H H
1-52 H H H Me 2 —(CH2)5-(4-Me-cHx) H H
1-53 H H H Me 2 —(CH2)5-(3-Et-cHx) H H
1-54 H H H Me 2 —(CH2)5-(4-Et-cHx) H H
1-55 H H H Me 2 —(CH2)5-(3-Pr-cHx) H H
1-56 H H H Me 2 —(CH2)5-(4-Pr-cHx) H H
1-57 H H H Me 2 —(CH2)5-(4-iPr-cHx) H H
1-58 H H H Me 2 —(CH2)5-(3-Bu-cHx) H H
1-59 H H H Me 2 —(CH2)5-(4-Bu-cHx) H H
1-60 H H H Me 2 —(CH2)5-(3-CF3-cHx) H H
1-61 H H H Me 2 —(CH2)5-(4-CF3-cHx) H H
1-62 H H H Me 2 —(CH2)5-(3-MeO-cHx) H H
1-63 H H H Me 2 —(CH2)5-(4-MeO-cHx) H H
1-64 H H H Me 2 —(CH2)5-(3-EtO-cHx) H H
1-65 H H H Me 2 —(CH2)5-(4-EtO-cHx) H H
1-66 H H H Me 2 —(CH2)5-(3-PrO-cHx) H H
1-67 H H H Me 2 —(CH2)5-(4-PrO-cHx) H H
1-68 H H H Me 2 —(CH2)5-(3-iPrO-cHx) H H
1-69 H H H Me 2 —(CH2)5-(4-iPrO-cHx) H H
1-70 H H H Me 2 —(CH2)5-[3-(2-Et—PrO)-cHx] H H
1-71 H H H Me 2 —(CH2)5-[4-(2-Et—PrO)-cHx] H H
1-72 H H H Me 2 —(CH2)5-(3-iBuO-cHx) H H
1-73 H H H Me 2 —(CH2)5-(4-iBuO-cHx) H H
1-74 H H H Me 2 —(CH2)5-(3-MeS-cHx) H H
1-75 H H H Me 2 —(CH2)5-(4-MeS-cHx) H H
1-76 H H H Me 2 —(CH2)5-(3-EtS-cHx) H H
1-77 H H H Me 2 —(CH2)5-(4-EtS-cHx) H H
1-78 H H H Me 2 —(CH2)5-(3-PrS-cHx) H H
1-79 H H H Me 2 —(CH2)5-(4-PrS-cHx) H H
1-80 H H H Me 2 —(CH2)5-(3-iPrS-cHx) H H
1-81 H H H Me 2 —(CH2)5-(4-iPrS-cHx) H H
1-82 H H H Me 2 —(CH2)5-[3-(2-Et—PrS)-cHx] H H
1-83 H H H Me 2 —(CH2)5-[4-(2-Et—PrS)-cHx] H H
1-84 H H H Me 2 —(CH2)5-(3-iBuS-cHx) H H
1-85 H H H Me 2 —(CH2)5-(4-iBuS-cHx) H H
1-86 H H H Me 2 —(CH2)5-(3-cHx-cHx) H H
1-87 H H H Me 2 —(CH2)5-(4-cHx-cHx) H H
1-88 H H H Me 2 —(CH2)5-(3-Ph-cHx) H H
1-89 H H H Me 2 —(CH2)5-(4-Ph-cHx) H H
1-90 H H H Me 2 —(CH2)5-(2,4-diMe-cHx) H H
1-91 H H H Me 2 —(CH2)5-(3,4-diMe-cHx) H H
1-92 H H H Me 2 —(CH2)5-(3,5-diMe-cHx) H H
1-93 H H H Me 2 —(CH2)5—Ph H H
1-94 H H H Me 2 —(CH2)5—Ph Me H
1-95 H H H Me 2 —(CH2)5—Ph H Me
1-96 H H H Me 2 —(CH2)5—Ph F H
1-97 H H H Me 2 —(CH2)5—Ph H F
1-98 H H H Me 2 —(CH2)5-(3-F—Ph) H H
1-99 H H H Me 2 —(CH2)5-(4-F—Ph) H H
1-100 H H H Me 2 —(CH2)5-(4-Cl—Ph) H H
1-101 H H H Me 2 —(CH2)5-(4-Br—Ph) H H
1-102 H H H Me 2 —(CH2)5-(3-Me—Ph) H H
1-103 H H H Me 2 —(CH2)5-(4-Me—Ph) H H
1-104 H H H Me 2 —(CH2)5-(3-Et—Ph) H H
1-105 H H H Me 2 —(CH2)5-(4-Et—Ph) H H
1-106 H H H Me 2 —(CH2)5-(3-Pr—Ph) H H
1-107 H H H Me 2 —(CH2)5-(4-Pr—Ph) H H
1-108 H H H Me 2 —(CH2)5-(3-iPr—Ph) H H
1-109 H H H Me 2 —(CH2)5-(4-iPr—Ph) H H
1-110 H H H Me 2 —(CH2)5-(3-Bu—Ph) H H
1-111 H H H Me 2 —(CH2)5-(4-Bu—Ph) H H
1-112 H H H Me 2 —(CH2)5-(3-CF3—Ph) H H
1-113 H H H Me 2 —(CH2)5-(4-CF3—Ph) H H
1-114 H H H Me 2 —(CH2)5-(3-MeO—Ph) H H
1-115 H H H Me 2 —(CH2)5-(4-MeO—Ph) H H
1-116 H H H Me 2 —(CH2)5-(3-EtO—Ph) H H
1-117 H H H Me 2 —(CH2)5-(4-EtO—Ph) H H
1-118 H H H Me 2 —(CH2)5-(3-PrO—Ph) H H
1-119 H H H Me 2 —(CH2)5-(4-PrO—Ph) H H
1-120 H H H Me 2 —(CH2)5-(3-iPrO—Ph) H H
1-121 H H H Me 2 —(CH2)5-(4-iPrO—Ph) H H
1-122 H H H Me 2 —(CH2)5-[3-(2-Et—PrO)—Ph] H H
1-123 H H H Me 2 —(CH2)5-[4-(2-Et—PrO)—Ph] H H
1-124 H H H Me 2 —(CH2)5-(3-iBuO—Ph) H H
1-125 H H H Me 2 —(CH2)5-(4-iBuO—Ph) H H
1-126 H H H Me 2 —(CH2)5-(3-MeS—Ph) H H
1-127 H H H Me 2 —(CH2)5-(4-MeS—Ph) H H
1-128 H H H Me 2 —(CH2)5-(3-EtS—Ph) H H
1-129 H H H Me 2 —(CH2)5-(4-EtS—Ph) H H
1-130 H H H Me 2 —(CH2)5-(3-PrS—Ph) H H
1-131 H H H Me 2 —(CH2)5-(4-PrS—Ph) H H
1-132 H H H Me 2 —(CH2)5-(3-iPrS—Ph) H H
1-133 H H H Me 2 —(CH2)5-(4-iPrS—Ph) H H
1-134 H H H Me 2 —(CH2)5-[3-(2-Et—PrS)—Ph] H H
1-135 H H H Me 2 —(CH2)5-[4-(2-Et—PrS)—Ph] H H
1-136 H H H Me 2 —(CH2)5-(3-iBuS—Ph) H H
1-137 H H H Me 2 —(CH2)5-(4-iBuS—Ph) H H
1-138 H H H Me 2 —(CH2)5-(3-cHx-Ph) H H
1-139 H H H Me 2 —(CH2)5-(4-cHx-Ph) H H
1-140 H H H Me 2 —(CH2)5-(3-Ph—Ph) H H
1-141 H H H Me 2 —(CH2)5-(4-Ph—Ph) H H
1-142 H H H Me 2 —(CH2)5-(2,4-diMe—Ph) H H
1-143 H H H Me 2 —(CH2)5-(3,4-diMe—Ph) H H
1-144 H H H Me 2 —(CH2)5-(3,5-diMe—Ph) H H
1-145 H H H Me 2 —(CH2)5-Np(1) H H
1-146 H H H Me 2 —(CH2)5-Np(2) H H
1-147 H H H Me 2 —(CH2)6-cPn H H
1-148 H H H Me 2 —(CH2)6-cHx H H
1-149 H H H Me 2 —(CH2)6-cHx Me H
1-150 H H H Me 2 —(CH2)6-cHx H Me
1-151 H H H Me 2 —(CH2)6-cHx F H
1-152 H H H Me 2 —(CH2)6-cHx H F
1-153 H H H Me 2 —(CH2)6-(3-F-cHx) H H
1-154 H H H Me 2 —(CH2)6-(4-F-cHx) H H
1-155 H H H Me 2 —(CH2)6-(4-Cl-cHx) H H
1-156 H H H Me 2 —(CH2)6-(4-Br-cHx) H H
1-157 H H H Me 2 —(CH2)6-(3-Me-cHx) H H
1-158 H H H Me 2 —(CH2)6-(4-Me-cHx) H H
1-159 H H H Me 2 —(CH2)6-(3-Et-cHx) H H
1-160 H H H Me 2 —(CH2)6-(4-Et-cHx) H H
1-161 H H H Me 2 —(CH2)6-(3-Pr-cHx) H H
1-162 H H H Me 2 —(CH2)6-(4-Pr-cHx) H H
1-163 H H H Me 2 —(CH2)6-(4-iPr-cHx) H H
1-164 H H H Me 2 —(CH2)6-(3-Bu-cHx) H H
1-165 H H H Me 2 —(CH2)6-(4-Bu-cHx) H H
1-166 H H H Me 2 —(CH2)6-(3-CF3-cHx) H H
1-167 H H H Me 2 —(CH2)6-(4-CF3-cHx) H H
1-168 H H H Me 2 —(CH2)6-(3-MeO-cHx) H H
1-169 H H H Me 2 —(CH2)6-(4-MeO-cHx) H H
1-170 H H H Me 2 —(CH2)6-(3-EtO-cHx) H H
1-171 H H H Me 2 —(CH2)6-(4-EtO-cHx) H H
1-172 H H H Me 2 —(CH2)6-(3-PrO-cHx) H H
1-173 H H H Me 2 —(CH2)6-(4-PrO-cHx) H H
1-174 H H H Me 2 —(CH2)6-(3-iPrO-cHx) H H
1-175 H H H Me 2 —(CH2)6-(4-iPrO-cHx) H H
1-176 H H H Me 2 —(CH2)6-[3-(2-Et—PrO)-cHx] H H
1-177 H H H Me 2 —(CH2)6-[4-(2-Et—PrO)-cHx] H H
1-178 H H H Me 2 —(CH2)6-(3-iBuO-cHx) H H
1-179 H H H Me 2 —(CH2)6-(4-iBuO-cHx) H H
1-180 H H H Me 2 —(CH2)6-(3-MeS-cHx) H H
1-181 H H H Me 2 —(CH2)6-(4-MeS-cHx) H H
1-182 H H H Me 2 —(CH2)6-(3-EtS-cHx) H H
1-183 H H H Me 2 —(CH2)6-(4-EtS-cHx) H H
1-184 H H H Me 2 —(CH2)6-(3-PrS-cHx) H H
1-185 H H H Me 2 —(CH2)6-(4-PrS-cHx) H H
1-186 H H H Me 2 —(CH2)6-(3-iPrS-cHx) H H
1-187 H H H Me 2 —(CH2)6-(4-iPrS-cHx) H H
1-188 H H H Me 2 —(CH2)6-[3-(2-Et—PrS)-cHx] H H
1-189 H H H Me 2 —(CH2)6-[4-(2-Et—PrS)-cHx] H H
1-190 H H H Me 2 —(CH2)6-(3-iBuS-cHx) H H
1-191 H H H Me 2 —(CH2)6-(4-iBuS-cHx) H H
1-192 H H H Me 2 —(CH2)6-(3-cHx-cHx) H H
1-193 H H H Me 2 —(CH2)6-(4-cHx-cHx) H H
1-194 H H H Me 2 —(CH2)6-(3-Ph-cHx) H H
1-195 H H H Me 2 —(CH2)6-(4-Ph-cHx) H H
1-196 H H H Me 2 —(CH2)6-(2,4-diMe-cHx) H H
1-197 H H H Me 2 —(CH2)6-(3,4-diMe-cHx) H H
1-198 H H H Me 2 —(CH2)6-(3,5-diMe-cHx) H H
1-199 H H H Me 2 —(CH2)6—Ph H H
1-200 H H H Me 2 —(CH2)6—Ph Me H
1-201 H H H Me 2 —(CH2)6—Ph H Me
1-202 H H H Me 2 —(CH2)6—Ph F H
1-203 H H H Me 2 —(CH2)6—Ph H F
1-204 H H H Me 2 —(CH2)6-(3-F—Ph) H H
1-205 H H H Me 2 —(CH2)6-(4-F—Ph) H H
1-206 H H H Me 2 —(CH2)6-(4-Cl—Ph) H H
1-207 H H H Me 2 —(CH2)6-(4-Br—Ph) H H
1-208 H H H Me 2 —(CH2)6-(3-Me—Ph) H H
1-209 H H H Me 2 —(CH2)6-(4-Me—Ph) H H
1-210 H H H Me 2 —(CH2)6-(3-Et—Ph) H H
1-211 H H H Me 2 —(CH2)6-(4-Et—Ph) H H
1-212 H H H Me 2 —(CH2)6-(3-Pr—Ph) H H
1-213 H H H Me 2 —(CH2)6-(4-Pr—Ph) H H
1-214 H H H Me 2 —(CH2)6-(3-iPr—Ph) H H
1-215 H H H Me 2 —(CH2)6-(4-iPr—Ph) H H
1-216 H H H Me 2 —(CH2)6-(3-Bu—Ph) H H
1-217 H H H Me 2 —(CH2)6-(4-Bu—Ph) H H
1-218 H H H Me 2 —(CH2)6-(3-CF3—Ph) H H
1-219 H H H Me 2 —(CH2)6-(4-CF3—Ph) H H
1-220 H H H Me 2 —(CH2)6-(3-MeO—Ph) H H
1-221 H H H Me 2 —(CH2)6-(4-MeO—Ph) H H
1-222 H H H Me 2 —(CH2)6-(3-EtO—Ph) H H
1-223 H H H Me 2 —(CH2)6-(4-EtO—Ph) H H
1-224 H H H Me 2 —(CH2)6-(3-PrO—Ph) H H
1-225 H H H Me 2 —(CH2)6-(4-PrO—Ph) H H
1-226 H H H Me 2 —(CH2)6-(3-iPrO—Ph) H H
1-227 H H H Me 2 —(CH2)6-(4-iPrO—Ph) H H
1-228 H H H Me 2 —(CH2)6-[3-(2-Et—PrO)—Ph] H H
1-229 H H H Me 2 —(CH2)6-[4-(2-Et—PrO)—Ph] H H
1-230 H H H Me 2 —(CH2)6-(3-iBuO—Ph) H H
1-231 H H H Me 2 —(CH2)6-(4-iBuO—Ph) H H
1-232 H H H Me 2 —(CH2)6-(3-MeS—Ph) H H
1-233 H H H Me 2 —(CH2)6-(4-MeS—Ph) H H
1-234 H H H Me 2 —(CH2)6-(3-EtS—Ph) H H
1-235 H H H Me 2 —(CH2)6-(4-EtS—Ph) H H
1-236 H H H Me 2 —(CH2)6-(3-PrS—Ph) H H
1-237 H H H Me 2 —(CH2)6-(4-PrS—Ph) H H
1-238 H H H Me 2 —(CH2)6-(3-iPrS—Ph) H H
1-239 H H H Me 2 —(CH2)6-(4-iPrS—Ph) H H
1-240 H H H Me 2 —(CH2)6-[3-(2-Et—PrS)—Ph] H H
1-241 H H H Me 2 —(CH2)6-[4-(2-Et—PrS)—Ph] H H
1-242 H H H Me 2 —(CH2)6-(3-iBuS—Ph) H H
1-243 H H H Me 2 —(CH2)6-(4-iBuS—Ph) H H
1-244 H H H Me 2 —(CH2)6-(3-cHx-Ph) H H
1-245 H H H Me 2 —(CH2)6-(4-cHx-Ph) H H
1-246 H H H Me 2 —(CH2)6-(3-Ph—Ph) H H
1-247 H H H Me 2 —(CH2)6-(4-Ph—Ph) H H
1-248 H H H Me 2 —(CH2)6-(2,4-diMe—Ph) H H
1-249 H H H Me 2 —(CH2)6-(3,4-diMe—Ph) H H
1-250 H H H Me 2 —(CH2)6-(3,5-diMe—Ph) H H
1-251 H H H Me 2 —(CH2)6-Np(1) H H
1-252 H H H Me 2 —(CH2)6-Np(2) H H
1-253 H H H Me 2 —(CH2)7-cHx H H
1-254 H H H Me 2 —(CH2)7-(4-F-cHx) H H
1-255 H H H Me 2 —(CH2)7-(4-Me-cHx) H H
1-256 H H H Me 2 —(CH2)7-(4-Et-cHx) H H
1-257 H H H Me 2 —(CH2)7-(4-CF3-cHx) H H
1-258 H H H Me 2 —(CH2)7-(4-MeO-cHx) H H
1-259 H H H Me 2 —(CH2)7-(4-EtO-cHx) H H
1-260 H H H Me 2 —(CH2)7-(4-MeS-cHx) H H
1-261 H H H Me 2 —(CH2)7-(4-cHx-cHx) H H
1-262 H H H Me 2 —(CH2)7-(4-Ph-cHx) H H
1-263 H H H Me 2 —(CH2)7-Ph H H
1-264 H H H Me 2 —(CH2)7-(4-F—Ph) H H
1-265 H H H Me 2 —(CH2)7- (4-Me—Ph) H H
1-266 H H H Me 2 —(CH2)7-(4-Et—Ph) H H
1-267 H H H Me 2 —(CH2)7-(4-CF3—Ph) H H
1-268 H H H Me 2 —(CH2)7-(4-MeO—Ph) H H
1-269 H H H Me 2 —(CH2)7-(4-EtO—Ph) H H
1-270 H H H Me 2 —(CH2)7-(4-MeS—Ph) H H
1-271 H H H Me 2 —(CH2)7-(4-cHx-Ph) H H
1-272 H H H Me 2 —(CH2)7-(4-Ph—Ph) H H
1-273 H H H Me 2 —(CH2)3—O-cHx H H
1-274 H H H Me 2 —(CH2)3—O-(4-F-cHx) H H
1-275 H H H Me 2 —(CH2)3—O-(4-Me-cHx) H H
1-276 H H H Me 2 —(CH2)3—O-(4-Et-cHx) H H
1-277 H H H Me 2 —(CH2)3—O-(4-CF3-cHx) H H
1-278 H H H Me 2 —(CH2)3—O-(4-MeO-cHx) H H
1-279 H H H Me 2 —(CH2)3—O-(4-EtO-cHx) H H
1-280 H H H Me 2 —(CH2)3—O-(4-MeS-cHx) H H
1-281 H H H Me 2 —(CH2)3—O-(4-cHx-cHx) H H
1-282 H H H Me 2 —(CH2)3—O-(4-Ph-cHx) H H
1-283 H H H Me 2 —(CH2)3—O—Ph H H
1-284 H H H Me 2 —(CH2)3—O-(4-F—Ph) H H
1-285 H H H Me 2 —(CH2)3—O-(4-Me—Ph) H H
1-286 H H H Me 2 —(CH2)3—O-(4-Et—Ph) H H
1-287 H H H Me 2 —(CH2)3—O-(4-CF3—Ph) H H
1-288 H H H Me 2 —(CH2)3—O-(4-MeO—Ph) H H
1-289 H H H Me 2 —(CH2)3—O-(4-EtO—Ph) H H
1-290 H H H Me 2 —(CH2)3—O-(4-MeS—Ph) H H
1-291 H H H Me 2 —(CH2)3—O-(4-cHx-Ph) H H
1-292 H H H Me 2 —(CH2)3—O-(4-Ph—Ph) H H
1-293 H H H Me 2 —(CH2)4—O-cpn H H
1-294 H H H Me 2 —(CH2)4—O-cHx H H
1-295 H H H Me 2 —(CH2)4—O-cHx Me H
1-296 H H H Me 2 —(CH2)4—O-cHx H Me
1-297 H H H Me 2 —(CH2)4—O-cHx F H
1-298 H H H Me 2 —(CH2)4—O-cHx H F
1-299 H H H Me 2 —(CH2)4—O-(3-F-cHx) H H
1-300 H H H Me 2 —(CH2)4—O-(4-F-cHx) H H
1-301 H H H Me 2 —(CH2)4—O-(4-Cl-cHx) H H
1-302 H H H Me 2 —(CH2)4—O-(4-Br-cHx) H H
1-303 H H H Me 2 —(CH2)4—O-(3-Me-cHx) H H
1-304 H H H Me 2 —(CH2)4—O-(4-Me-cHx) H H
1-305 H H H Me 2 —(CH2)4—O-(3-Et-cHx) H H
1-306 H H H Me 2 —(CH2)4—O-(4-Et-cHx) H H
1-307 H H H Me 2 —(CH2)4—O-(3-Pr-cHx) H H
1-308 H H H Me 2 —(CH2)4—O-(4-Pr-cHx) H H
1-309 H H H Me 2 —(CH2)4—O-(4-iPr-cHx) H H
1-310 H H H Me 2 —(CH2)4—O-(3-Bu-cHx) H H
1-311 H H H Me 2 —(CH2)4—O-(4-Bu-cHx) H H
1-312 H H H Me 2 —(CH2)4—O-(3-CF3-cHx) H H
1-313 H H H Me 2 —(CH2)4—O-(4-CF3-cHx) H H
1-314 H H H Me 2 —(CH2)4—O-(3-MeO-cHx) H H
1-315 H H H Me 2 —(CH2)4—O-(4-MeO-cHx) H H
1-316 H H H Me 2 —(CH2)4—O-(3-EtO-cHx) H H
1-317 H H H Me 2 —(CH2)4—O-(4-EtO-cHx) H H
1-318 H H H Me 2 —(CH2)4—O-(3-PrO-cHx) H H
1-319 H H H Me 2 —(CH2)4—O-(4-PrO-cHx) H H
1-320 H H H Me 2 —(CH2)4—O-(3-iPrO-cHx) H H
1-321 H H H Me 2 —(CH2)4—O-(4-iPrO-cHx) H H
1-322 H H H Me 2 —(CH2)4—O-[3-(2-Et—PrO)-cHx] H H
1-323 H H H Me 2 —(CH2)4—O-[4-(2-Et—PrO)-cHx] H H
1-324 H H H Me 2 —(CH2)4—O-(3-iBuO-cHx) H H
1-325 H H H Me 2 —(CH2)4—O-(4-iBuO-cHx) H H
1-326 H H H Me 2 —(CH2)4—O-(3-MeS-cHx) H H
1-327 H H H Me 2 —(CH2)4—O-(4-MeS-cHx) H H
1-328 H H H Me 2 —(CH2)4—O-(3-EtS-cHx) H H
1-329 H H H Me 2 —(CH2)4—O-(4-EtS-cHx) H H
1-330 H H H Me 2 —(CH2)4—O-(3-PrS-cHx) H H
1-331 H H H Me 2 —(CH2)4—O-(4-PrS-cHx) H H
1-332 H H H Me 2 —(CH2)4—O-(3-iPrS-cHx) H H
1-333 H H H Me 2 —(CH2)4—O-(4-iPrS-cHx) H H
1-334 H H H Me 2 —(CH2)4—O-[3-(2-Et—PrS)-cHx] H H
1-335 H H H Me 2 —(CH2)4—O-[4-(2-Et—PrS)-cHx] H H
1-336 H H H Me 2 —(CH2)4—O-(3-iBuS-cHx) H H
1-337 H H H Me 2 —(CH2)4—O-(4-iBuS-cHx) H H
1-338 H H H Me 2 —(CH2)4—O-(3-cHx-cHx) H H
1-339 H H H Me 2 —(CH2)4—O-(4-cHx-cHx) H H
1-340 H H H Me 2 —(CH2)4—O-(3-Ph-cHx) H H
1-341 H H H Me 2 —(CH2)4—O-(4-Ph-cHx) H H
1-342 H H H Me 2 —(CH2)4—O-(2,4-diMe-cHx) H H
1-343 H H H Me 2 —(CH2)4—O-(3,4-diMe-cHx) H H
1-344 H H H Me 2 —(CH2)4—O-(3,5-diMe-cHx) H H
1-345 H H H Me 2 —(CH2)4—O—Ph H H
1-346 H H H Me 2 —(CH2)4—O—Ph Me H
1-347 H H H Me 2 —(CH2)4—O—Ph H Me
1-348 H H H Me 2 —(CH2)4—O—Ph F H
1-349 H H H Me 2 —(CH2)4—O—Ph H F
1-350 H H H Me 2 —(CH2)4—O-(3-F—Ph) H H
1-351 H H H Me 2 —(CH2)4—O-(4-F—Ph) H H
1-352 H H H Me 2 —(CH2)4—O-(4-Cl—Ph) H H
1-353 H H H Me 2 —(CH2)4—O-(4-Br—Ph) H H
1-354 H H H Me 2 —(CH2)4—O-(3-Me—Ph) H H
1-355 H H H Me 2 —(CH2)4—O-(4-Me—Ph) H H
1-356 H H H Me 2 —(CH2)4—O-(3-Et—Ph) H H
1-357 H H H Me 2 —(CH2)4—O-(4-Et—Ph) H H
1-358 H H H Me 2 —(CH2)4—O-(3-Pr—Ph) H H
1-359 H H H Me 2 —(CH2)4—O-(4-Pr—Ph) H H
1-360 H H H Me 2 —(CH2)4—O-(3-iPr—Ph) H H
1-361 H H H Me 2 —(CH2)4—O-(4-iPr—Ph) H H
1-362 H H H Me 2 —(CH2)4—O-(3-Bu—Ph) H H
1-363 H H H Me 2 —(CH2)4—O-(4-Bu—Ph) H H
1-364 H H H Me 2 —(CH2)4—O-(3-CF3—Ph) H H
1-365 H H H Me 2 —(CH2)4—O-(4-CF3—Ph) H H
1-366 H H H Me 2 —(CH2)4—O-(3-MeO—Ph) H H
1-367 H H H Me 2 —(CH2)4—O-(4-MeO—Ph) H H
1-368 H H H Me 2 —(CH2)4—O-(3-EtO—Ph) H H
1-369 H H H Me 2 —(CH2)4—O-(4-EtO—Ph) H H
1-370 H H H Me 2 —(CH2)4—O-(3-PrO—Ph) H H
1-371 H H H Me 2 —(CH2)4—O-(4-PrO—Ph) H H
1-372 H H H Me 2 —(CH2)4—O-(3-iPrO—Ph) H H
1-373 H H H Me 2 —(CH2)4—O-(4-iPrO—Ph) H H
1-374 H H H Me 2 —(CH2)4—O-[3-(2-Et—PrO)—Ph] H H
1-375 H H H Me 2 —(CH2)4—O-[4-(2-Et—PrO)—Ph] H H
1-376 H H H Me 2 —(CH2)4—O-(3-iBuO—Ph) H H
1-377 H H H Me 2 —(CH2)4—O-(4-iBuO—Ph) H H
1-378 H H H Me 2 —(CH2)4—O-(3-MeS—Ph) H H
1-379 H H H Me 2 —(CH2)4—O-(4-MeS—Ph) H H
1-380 H H H Me 2 —(CH2)4—O-(3-EtS—Ph) H H
1-381 H H H Me 2 —(CH2)4—O-(4-EtS—Ph) H H
1-382 H H H Me 2 —(CH2)4—O-(3-PrS—Ph) H H
1-383 H H H Me 2 —(CH2)4—O-(4-PrS—Ph) H H
1-384 H H H Me 2 —(CH2)4—O-(3-iPrS—Ph) H H
1-385 H H H Me 2 —(CH2)4—O-(4-iPrS—Ph) H H
1-386 H H H Me 2 —(CH2)4—O-[3-(2-Et—PrS)—Ph] H H
1-387 H H H Me 2 —(CH2)4—O-[4-(2-Et—PrS)—Ph] H H
1-388 H H H Me 2 —(CH2)4—O-(3-iBuS—Ph) H H
1-389 H H H Me 2 —(CH2)4—O-(4-iBuS—Ph) H H
1-390 H H H Me 2 —(CH2)4—O-(3-cHx-Ph) H H
1-391 H H H Me 2 —(CH2)4—O-(4-cHx-Ph) H H
1-392 H H H Me 2 —(CH2)4—O-(3-Ph—Ph) H H
1-393 H H H Me 2 —(CH2)4—O-(4-Ph—Ph) H H
1-394 H H H Me 2 —(CH2)4—O-(2,4-diMe—Ph) H H
1-395 H H H Me 2 —(CH2)4—O-(3,4-diMe—Ph) H H
1-396 H H H Me 2 —(CH2)4—O-(3,5-diMe—Ph) H H
1-397 H H H Me 2 —(CH2)5—O-cHx H H
1-398 H H H Me 2 —(CH2)5—O—Ph H H
1-399 H H H Me 2 —(CH2)6—O-cHx H H
1-400 H H H Me 2 —(CH2)6—O—Ph H H
1-401 H H H Me 2 —(CH2)3—OCH2-cHx H H
1-402 H H H Me 2 —(CH2)3—OCH2-(4-F-cHx) H H
1-403 H H H Me 2 —(CH2)3—OCH2-(4-Me-cHx) H H
1-404 H H H Me 2 —(CH2)3—OCH2-(4-Et-cHx) H H
1-405 H H H Me 2 —(CH2)3—OCH2-(4-CF3-cHx) H H
1-406 H H H Me 2 —(CH2)3—OCH2-(4-MeO-cHx) H H
1-407 H H H Me 2 —(CH2)3—OCH2-(4-EtO-cHx) H H
1-408 H H H Me 2 —(CH2)3—OCH2-(4-MeS-cHx) H H
1-409 H H H Me 2 —(CH2)3—OCH2-(4-cHx-cHx) H H
1-410 H H H Me 2 —(CH2)3—OCH2-(4-Ph-cHx) H H
1-411 H H H Me 2 —(CH2)3—OCH2—Ph H H
1-412 H H H Me 2 —(CH2)3—OCH2-(4-F—Ph) H H
1-413 H H H Me 2 —(CH2)3—OCH2-(4-Me—Ph) H H
1-414 H H H Me 2 —(CH2)3—OCH2-(4-Et—Ph) H H
1-415 H H H Me 2 —(CH2)3—OCH2-(4-CF3—Ph) H H
1-426 H H H Me 2 —(CH2)3—OCH2-(4-MeO—Ph) H H
1-427 H H H Me 2 —(CH2)3—OCH2-(4-EtO—Ph) H H
1-428 H H H Me 2 —(CH2)3—OCH2-(4-MeS—Ph) H H
1-429 H H H Me 2 —(CH2)3—OCH2-(4-cHx-Ph) H H
1-420 H H H Me 2 —(CH2)3—OCH2-(4-Ph—Ph) H H
1-421 H H H Me 2 —(CH2)4—OCH2-cPn H H
1-422 H H H Me 2 —(CH2)4—OCH2-cHx H H
1-423 H H H Me 2 —(CH2)4—OCH2-cHx Me H
1-424 H H H Me 2 —(CH2)4—OCH2-cHx H Me
1-425 H H H Me 2 —(CH2)4—OCH2-cHx F H
1-426 H H H Me 2 —(CH2)4—OCH2-cHx H F
1-427 H H H Me 2 —(CH2)4—OCH2-(3-F-cHx) H H
1-428 H H H Me 2 —(CH2)4—OCH2-(4-F-cHx) H H
1-429 H H H Me 2 —(CH2)4—OCH2-(4-Cl-cHx) H H
1-430 H H H Me 2 —(CH2)4—OCH2-(4-Br-cHx) H H
1-431 H H H Me 2 —(CH2)4—OCH2-(3-Me-cHx) H H
1-432 H H H Me 2 —(CH2)4—OCH2-(4-Me-cHx) H H
1-433 H H H Me 2 —(CH2)4—OCH2-(3-Et-cHx) H H
1-434 H H H Me 2 —(CH2)4—OCH2-(4-Et-cHx) H H
1-435 H H H Me 2 —(CH2)4—OCH2-(3-Pr-cHx) H H
1-436 H H H Me 2 —(CH2)4—OCH2-(4-Pr-cHx) H H
1-437 H H H Me 2 —(CH2)4—OCH2-(4-iPr-cHx) H H
1-438 H H H Me 2 —(CH2)4—OCH2-(3-Bu-cHx) H H
1-439 H H H Me 2 —(CH2)4—OCH2-(4-Bu-cHx) H H
1-440 H H H Me 2 —(CH2)4—OCH2-(3-CF3-cHx) H H
1-441 H H H Me 2 —(CH2)4—OCH2-(4-CF3-cHx) H H
1-442 H H H Me 2 —(CH2)4—OCH2-(3-MeO-cHx) H H
1-443 H H H Me 2 —(CH2)4—OCH2-(4-MeO-cHx) H H
1-444 H H H Me 2 —(CH2)4—OCH2-(3-EtO-cHx) H H
1-445 H H H Me 2 —(CH2)4—OCH2-(4-EtO-cHx) H H
1-446 H H H Me 2 —(CH2)4—OCH2-(3-PrO-cHx) H H
1-447 H H H Me 2 —(CH2)4—OCH2-(4-PrO-cHx) H H
1-448 H H H Me 2 —(CH2)4—OCH2-(3-iPrO-cHx) H H
1-449 H H H Me 2 —(CH2)4—OCH2-(4-iPrO-cHx) H H
1-450 H H H Me 2 —(CH2)4—OCH2-[3-(2-Et—PrO)-cHx] H H
1-451 H H H Me 2 —(CH2)4—OCH2-[4-(2-Et—PrO)-cHx] H H
1-452 H H H Me 2 —(CH2)4—OCH2-(3-iBuO-cHx) H H
1-453 H H H Me 2 —(CH2)4—OCH2-(4-iBuO-cHx) H H
1-454 H H H Me 2 —(CH2)4—OCH2-(3-MeS-cHx) H H
1-455 H H H Me 2 —(CH2)4—OCH2-(4-MeS-cHx) H H
1-456 H H H Me 2 —(CH2)4—OCH2-(3-EtS-cHx) H H
1-457 H H H Me 2 —(CH2)4—OCH2-(4-EtS-cHx) H H
1-458 H H H Me 2 —(CH2)4—OCH2-(3-PrS-cHx) H H
1-459 H H H Me 2 —(CH2)4—OCH2-(4-PrS-cHx) H H
1-460 H H H Me 2 —(CH2)4—OCH2-(3-iPrS-cHx) H H
1-461 H H H Me 2 —(CH2)4—OCH2-(4-iPrS-cHx) H H
1-462 H H H Me 2 —(CH2)4—OCH2-[3-(2-Et—PrS)-cHx] H H
1-463 H H H Me 2 —(CH2)4—OCH2-[4-(2-Et—PrS)-cHx] H H
1-464 H H H Me 2 —(CH2)4—OCH2-(3-iBuS-cHx) H H
1-465 H H H Me 2 —(CH2)4—OCH2-(4-iBuS-cHx) H H
1-466 H H H Me 2 —(CH2)4—OCH2-(3-cHx-cHx) H H
1-467 H H H Me 2 —(CH2)4—OCH2-(4-cHx-cHx) H H
1-468 H H H Me 2 —(CH2)4—OCH2-(3-Ph-cHx) H H
1-469 H H H Me 2 —(CH2)4—OCH2-(4-Ph-cHx) H H
1-470 H H H Me 2 —(CH2)4—OCH2-(2,4-diMe-cHx) H H
1-471 H H H Me 2 —(CH2)4—OCH2-(3,4-diMe-cHx) H H
1-472 H H H Me 2 —(CH2)4—OCH2-(3,5-diMe-cHx) H H
1-473 H H H Me 2 —(CH2)4—OCH2—Ph H H
1-474 H H H Me 2 —(CH2)4—OCH2—Ph Me H
1-475 H H H Me 2 —(CH2)4—OCH2—Ph H Me
1-476 H H H Me 2 —(CH2)4—OCH2—Ph F H
1-477 H H H Me 2 —(CH2)4—OCH2—Ph H F
1-478 H H H Me 2 —(CH2)4—OCH2-(3-F—Ph) H H
1-479 H H H Me 2 —(CH2)4—OCH2-(4-F—Ph) H H
1-480 H H H Me 2 —(CH2)4—OCH2-(4-Cl—Ph) H H
1-481 H H H Me 2 —(CH2)4—OCH2-(4-Br—Ph) H H
1-482 H H H Me 2 —(CH2)4—OCH2-(3-Me—Ph) H H
1-483 H H H Me 2 —(CH2)4—OCH2-(4-Me—Ph) H H
1-484 H H H Me 2 —(CH2)4—OCH2-(3-Et—Ph) H H
1-485 H H H Me 2 —(CH2)4—OCH2-(4-Et—Ph) H H
1-486 H H H Me 2 —(CH2)4—OCH2-(3-Pr—Ph) H H
1-487 H H H Me 2 —(CH2)4—OCH2-(4-Pr—Ph) H H
1-488 H H H Me 2 —(CH2)4—OCH2-(3-iPr—Ph) H H
1-489 H H H Me 2 —(CH2)4—OCH2-(4-ipr—Ph) H H
1-490 H H H Me 2 —(CH2)4—OCH2-(3-Bu—Ph) H H
1-491 H H H Me 2 —(CH2)4—OCH2-(4-Bu—Ph) H H
1-492 H H H Me 2 —(CH2)4—OCH2-(3-CF3—Ph) H H
1-493 H H H Me 2 —(CH2)4—OCH2-(4-CF3—Ph) H H
1-494 H H H Me 2 —(CH2)4—OCH2-(3-MeO—Ph) H H
1-495 H H H Me 2 —(CH2)4—OCH2-(4-MeO—Ph) H H
1-496 H H H Me 2 —(CH2)4—OCH2-(3-EtO—Ph) H H
1-497 H H H Me 2 —(CH2)4—OCH2-(4-EtO—Ph) H H
1-498 H H H Me 2 —(CH2)4—OCH2-(3-PrO—Ph) H H
1-499 H H H Me 2 —(CH2)4—OCH2-(4-PrO—Ph) H H
1-500 H H H Me 2 —(CH2)4—OCH2-(3-iPrO—Ph) H H
1-501 H H H Me 2 —(CH2)4—OCH2-(4-iPrO—Ph) H H
1-502 H H H Me 2 —(CH2)4—OCH2-[3-(2-Et—PrO)—Ph] H H
1-503 H H H Me 2 —(CH2)4—OCH2-[4-(2-Et—PrO)—Ph] H H
1-504 H H H Me 2 —(CH2)4—OCH2-(3-iBuO—Ph) H H
1-505 H H H Me 2 —(CH2)4—OCH2-(4-iBuO—Ph) H H
1-506 H H H Me 2 —(CH2)4—OCH2-(3-MeS—Ph) H H
1-507 H H H Me 2 —(CH2)4—OCH2-(4-MeS—Ph) H H
1-508 H H H Me 2 —(CH2)4—OCH2-(3-EtS—Ph) H H
1-509 H H H Me 2 —(CH2)4—OCH2-(4-EtS—Ph) H H
1-510 H H H Me 2 —(CH2)4—OCH2-(3-PrS—Ph) H H
1-511 H H H Me 2 —(CH2)4—OCH2-(4-PrS—Ph) H H
1-512 H H H Me 2 —(CH2)4—OCH2-(3-iPrS—Ph) H H
1-513 H H H Me 2 —(CH2)4—OCH2-(4-iPrS—Ph) H H
1-514 H H H Me 2 —(CH2)4—OCH2-[3-(2-Et—PrS)—Ph] H H
1-515 H H H Me 2 —(CH2)4—OCH2-[4-(2-Et—PrS)—Ph] H H
1-516 H H H Me 2 —(CH2)4—OCH2-(3-iBuS—Ph) H H
1-517 H H H Me 2 —(CH2)4—OCH2-(4-iBuS—Ph) H H
1-518 H H H Me 2 —(CH2)4—OCH2-(3-cHx-Ph) H H
1-519 H H H Me 2 —(CH2)4—OCH2-(4-cHx-Ph) H H
1-520 H H H Me 2 —(CH2)4—OCH2-(3-Ph—Ph) H H
1-521 H H H Me 2 —(CH2)4—OCH2-(4-Ph—Ph) H H
1-522 H H H Me 2 —(CH2)4—OCH2-(2,4-diMe—Ph) H H
1-523 H H H Me 2 —(CH2)4—OCH2-(3,4—diMe—Ph) H H
1-524 H H H Me 2 —(CH2)4—OCH2-(3,5-diMe—Ph) H H
1-525 H H H Me 2 —(CH2)5—OCH2-cHx H H
1-526 H H H Me 2 —(CH2)5—OCH2—Ph H H
1-527 H H H Me 2 —(CH2)6—OCH2-cHx H H
1-528 H H H Me 2 —(CH2)6—OCH2—Ph H H
1-529 H H H Me 2 —C≡C-cHx H H
1-530 H H H Me 2 —C≡C-(4-F-cHx) H H
1-531 H H H Me 2 —C≡C-(4-Me-cHx) H H
1-532 H H H Me 2 —C≡C-(4-Et-cHx) H H
1-533 H H H Me 2 —C≡C-(4-CF3-cHx) H H
1-534 H H H Me 2 —C≡C-(4-MeO-cHx) H H
1-535 H H H Me 2 —C≡C-(4-EtO-cHx) H H
1-536 H H H Me 2 —C≡C-(4-MeS-dHx) H H
1-537 H H H Me 2 —C≡C-(4-cHx-cHx) H H
1-538 H H H Me 2 —C≡C-(4-Ph-cHx) H H
1-539 H H H Me 2 —C≡C—Ph H H
1-540 H H H Me 2 —C≡C-(4-F—Ph) H H
1-541 H H H Me 2 —C≡C-(4-Me—Ph) H H
1-542 H H H Me 2 —C≡C-(4-Pr—Ph) H H
1-543 H H H Me 2 —C≡C-(4-Bu—Ph) H H
1-544 H H H Me 2 —C≡C-(4-MeO—Ph) H H
1-545 H H H Me 2 —C≡C-(4-EtO—Ph) H H
1-546 H H H Me 2 —C≡C-(4-PrO—Ph) H H
1-547 H H H Me 2 —C≡C-(4-cHx-Ph) H H
1-548 H H H Me 2 —C≡C-(4-Ph—Ph) H H
1-549 H H H Me 2 —C≡C—(CH2)2-cHx H H
1-550 H H H Me 2 —C≡C—(CH2)2-(4-F-cHx) H H
1-551 H H H Me 2 —C≡C—(CH2)2-(4-Me-cHx) H H
1-552 H H H Me 2 —C≡C—(CH2)2-(4-Et-cHx) H H
1-553 H H H Me 2 —C≡C—(CH2)2-(4-CF3-cHx) H H
1-554 H H H Me 2 —C≡C—(CH2)2-(4-MeO-cHx) H H
1-555 H H H Me 2 —C≡C—(CH2)2-(4-EtO-cHx) H H
1-556 H H H Me 2 —C≡C—(CH2)2-(4-MeS-cHx) H H
1-557 H H H Me 2 —C≡C—(CH2)2-(4-cHx-cHx) H H
1-558 H H H Me 2 —C≡C—(CH2)2-(4-Ph-cHx) H H
1-559 H H H Me 2 —C≡C—(CH2)2—Ph H H
1-560 H H H Me 2 —C≡C—(CH2)2-(4-F—Ph) H H
1-561 H H H Me 2 —C≡C—(CH2)2-(4-Me—Ph) H H
1-562 H H H Me 2 —C≡C—(CH2)2-(4-Et—Ph) H H
1-563 H H H Me 2 —C≡C—(CH2)2~(4-CF3—Ph) H H
1-564 H H H Me 2 —C≡C—(CH2)2-(4-MeO—Ph) H H
1-565 H H H Me 2 —C≡C—(CH2)2-(4-EtO—Ph) H H
1-566 H H H Me 2 —C≡C—(CH2)2-(4-MeS—Ph) H H
1-567 H H H Me 2 —C≡C—(CH2)2-(4-cHx-Ph) H H
1-568 H H H Me 2 —C≡C—(CH2)2-(4-Ph—Ph) H H
1-569 H H H Me 2 —C≡C—(CH2)3-cPn H H
1-570 H H H Me 2 —C≡C—(CH2)3-cHx H H
1-571 H H H Me 2 —C≡C—(CH2)3-cHx Me H
1-572 H H H Me 2 —C≡C—(CH2)3-cHx H Me
1-573 H H H Me 2 —C≡C—(CH2)3-cHx F H
1-574 H H H Me 2 —C≡C—(CH2)3-cHx H F
1-575 H H H Me 2 —C≡C—(CH2)3-(3-F-cHx) H H
1-576 H H H Me 2 —C≡C—(CH2)3-(4-F-cHx) H H
1-577 H H H Me 2 —C≡C—(CH2)3-(4-Cl-cHx) H H
1-578 H H H Me 2 —C≡C—(CH2)3-(4-Br-cHx) H H
1-579 H H H Me 2 —C≡C—(CH2)3-(3-Me-cHx) H H
1-580 H H H Me 2 —C≡C—(CH2)3-(4-Me-cHx) H H
1-581 H H H Me 2 —C≡C—(CH2)3-(3-Et-cHx) H H
1-582 H H H Me 2 —C≡C—(CH2)3-(4-Et-cHx) H H
1-583 H H H Me 2 —C≡C—(CH2)3-(3-Pr-cHx) H H
1-584 H H H Me 2 —C≡C—(CH2)3-(4-Pr-cHx) H H
1-585 H H H Me 2 —C≡C—(CH2)3-(4-iPr-cHx) H H
1-586 H H H Me 2 —C≡C—(CH2)3-(3-Bu-cHx) H H
1-587 H H H Me 2 —C≡C—(CH2)3-(4-Bu-cHx) H H
1-588 H H H Me 2 —C≡C—(CH2)3-(3-CF3-cHx) H H
1-589 H H H Me 2 —C≡C—(CH2)3-(4-CF3-cHx) H H
1-590 H H H Me 2 —C≡C—(CH2)3-(3-MeO-cHx) H H
1-591 H H H Me 2 —C≡C—(CH2)3-(4-MeO-cHx) H H
1-592 H H H Me 2 —C≡C—(CH2)3-(3-EtO-cHx) H H
1-593 H H H Me 2 —C≡C—(CH2)3-(4-EtO-cHx) H H
1-594 H H H Me 2 —C≡C—(CH2)3-(3-PrO-cHx) H H
1-595 H H H Me 2 —C≡C—(CH2)3-(4-PrO-cHx) H H
1-596 H H H Me 2 —C≡C—(CH2)3-(3-iPrO-cHx) H H
1-597 H H H Me 2 —C≡C—(CH2)3-(4-iPrO-cHx) H H
1-598 H H H Me 2 —C≡C—(CH2)3-[3-(2-Et—Pro)-cHx] H H
1-599 H H H Me 2 —C≡C—(CH2)3-[4-(2-Et—Pro)-cHx] H H
1-600 H H H Me 2 —C≡C—(CH2)3-(3-iBuO-cHx) H H
1-601 H H H Me 2 —C≡C—(CH2)3-(4-iBuO-cHx) H H
1-602 H H H Me 2 —C≡C—(CH2)3-(3-MeS-cHx) H H
1-603 H H H Me 2 —C≡C—(CH2)3-(4-MeS-cHx) H H
1-604 H H H Me 2 —C≡C—(CH2)3-(3-EtS-cHx) H H
1-605 H H H Me 2 —C≡C—(CH2)3-(4-EtS-cHx) H H
1-606 H H H Me 2 —C≡C—(CH2)3-(3-PrS-cHx) H H
1-607 H H H Me 2 —C≡C—(CH2)3-(4-PrS-cHx) H H
1-608 H H H Me 2 —C≡C—(CH2)3-(3-iPrS-cHx) H H
1-609 H H H Me 2 —C≡C—(CH2)3-(4-iPrS-cHx) H H
1-610 H H H Me 2 —C≡C—(CH2)3-[3-(2-Et—PrS)-cHx] H H
1-611 H H H Me 2 —C≡C—(CH2)3-[4-(2-Et—PrS)-cHx] H H
1-612 H H H Me 2 —C≡C—(CH2)3-(3-iBuS-cHx) H H
1-613 H H H Me 2 —C≡C—(CH2)3-(4-iBuS-cHx) H H
1-614 H H H Me 2 —C≡C—(CH2)3-(3-cHx-cHx) H H
1-615 H H H Me 2 —C≡C—(CH2)3-(4-cHx-cHx) H H
1-616 H H H Me 2 —C≡C—(CH2)3-(3-Ph-cHx) H H
1-617 H H H Me 2 —C≡C—(CH2)3-(4-Ph-cHx) H H
1-618 H H H Me 2 —C≡C—(CH2)3-(2,4-diMe-cHx) H H
1-619 H H H Me 2 —C≡C—(CH2)3-(3,4-diMe-cHx) H H
1-620 H H H Me 2 —C≡C—(CH2)3-(3,5-diMe-cHx) H H
1-621 H H H Me 2 —C≡C—(CH2)3—Ph H H
1-622 H H H Me 2 —C≡C—(CH2)3—Ph Me H
1-623 H H H Me 2 —C≡C—(CH2)3—Ph H Me
1-624 H H H Me 2 —C≡C—(CH2)3—Ph F H
1-625 H H H Me 2 —C≡C—(CH2)3—Ph H F
1-626 H H H Me 2 —C≡C—(CH2)3-(3-F—Ph) H H
1 627 H H H Me 2 —C≡C—(CH2)3-(4-F—Ph) H H
1-628 H H H Me 2 —C≡C—(CH2)3-(4-Cl—Ph) H H
1-629 H H H Me 2 —C≡C—(CH2)3-(4-Br—Ph) H H
1-630 H H H Me 2 —C≡C—(CH2)3-(3-Me—Ph) H H
1-631 H H H Me 2 —C≡C—(CH2)3-(4-Me—Ph) H H
1-632 H H H Me 2 —C≡C—(CH2)3—(3-Et—Ph) H H
1-633 H H H Me 2 —C≡C—(CH2)3-(4-Et—Ph) H H
1-634 H H H Me 2 —C≡C—(CH2)3-(3-Pr—Ph) H H
1-635 H H H Me 2 —C≡C—(CH2)3-(4-Pr—Ph) H H
1-636 H H H Me 2 —C≡C—(CH2)3-(3-iPr—Ph) H H
1-637 H H H Me 2 —C≡C—(CH2)3-(4-iPr—Ph) H H
1-638 H H H Me 2 —C≡C—(CH2)3-(3-Bu—Ph) H H
1-639 H H H Me 2 —C≡C—(CH2)3—(4-Bu—Ph) H H
1-640 H H H Me 2 —C≡C—(CH2)3-(3-CF3—Ph) H H
1-641 H H H Me 2 —C≡C—(CH2)3-(4-CF3—Ph) H H
1-642 H H H Me 2 —C≡C—(CH2)3-(3-MeO—Ph) H H
1-643 H H H Me 2 —C≡C—(CH2)3-(4-MeO—Ph) H H
1-644 H H H Me 2 —C≡C—(CH2)3-(3-EtO—Ph) H H
1-645 H H H Me 2 —C≡C—(CH2)3-(4-EtO—Ph) H H
1-646 H H H Me 2 —C≡C—(CH2)3-(3-PrO—Ph) H H
1-647 H H H Me 2 —C≡C—(CH2)3-(4-PrO—Ph) H H
1-648 H H H Me 2 —C≡C—(CH2)3-(3-iPrO—Ph) H H
1-649 H H H Me 2 —C≡C—(CH2)3-(4-iPrO—Ph) H H
1-650 H H H Me 2 —C≡C—(CH2)3-[3-(2-Et—PrO)—Ph] H H
1-651 H H H Me 2 —C≡C—(CH2)3-[4-(2-Et—PrO)—Ph] H H
1-652 H H H Me 2 —C≡C—(CH2)3-(3-iBuO—Ph) H H
1-653 H H H Me 2 —C≡C—(CH2)3-(4-iBuO-Ph) H H
1-654 H H H Me 2 —C≡C—(CH2)3-(3-MeS—Ph) H H
1-655 H H H Me 2 —C≡C—(CH2)3-(4-MeS—Ph) H H
1-656 H H H Me 2 —C≡C—(CH2)3-(3-EtS—Ph) H H
1-657 H H H Me 2 —C≡C—(CH2)3-(4-EtS—Ph) H H
1-658 H H H Me 2 —C≡C—(CH2)3-(3-PrS—Ph) H H
1-659 H H H Me 2 —C≡C—(CH2)3-(4-PrS—Ph) H H
1-660 H H H Me 2 —C≡C—(CH2)3-(3-iPrS—Ph) H H
1-661 H H H Me 2 —C≡C—(CH2)3-(4-iPrS—Ph) H H
1-662 H H H Me 2 —C≡C—(CH2)3-[3-(2-Et—PrS)—Ph] H H
1-663 H H H Me 2 —C≡C—(CH2)3-[4-(2-Et—PrS)—Ph] H H
1-664 H H H Me 2 —C≡C—(CH2)3-(3-iBuS—Ph) H H
1-665 H H H Me 2 —C≡C—(CH2)3-(4-iBuS—Ph) H H
1-666 H H H Me 2 —C≡C—(CH2)3-(3-cHx-Ph) H H
1-667 H H H Me 2 —C≡C—(CH2)3-(4-cHx-Ph) H H
1-668 H H H Me 2 —C≡C—(CH2)3-(3-Ph—Ph) H H
1-669 H H H Me 2 —C≡C—(CH2)3-(4-Ph—Ph) H H
1-670 H H H Me 2 —C≡C—(CH2)3-(2,4-diMe—Ph) H H
1-671 H H H Me 2 —C≡C—(CH2)3-(3,4-diMe—Ph) H H
1-672 H H H Me 2 —C≡C—(CH2)3-(3,5-diMe—Ph) H H
1-673 H H H Me 2 —C≡C—(CH2)3-Np(1) H H
1-674 H H H Me 2 —C≡C—(CH2)3-Np(2) H H
1-675 H H H Me 2 —C≡C—(CH2)4-cPn H H
1-676 H H H Me 2 —C≡C—(CH2)4-cHx H H
1-677 H H H Me 2 —C≡C—(CH2)4-cHx Me H
1-678 H H H Me 2 —C≡C—(CH2)4-cHx H Me
1-679 H H H Me 2 —C≡C—(CH2)4-cHx F H
1-680 H H H Me 2 —C≡C—(CH2)4-cHx H F
1-681 H H H Me 2 —C≡C—(CH2)4-(3-F-cHx) H H
1-682 H H H Me 2 —C≡C—(CH2)4-(4-F-cHx) H H
1-683 H H H Me 2 —C≡C—(CH2)4-(4-Cl-cHx) H H
1-684 H H H Me 2 —C≡C—(CH2)4-(4-Br-cHx) H H
1-685 H H H Me 2 —C≡C—(CH2)4-(3-Me-cHx) H H
1-686 H H H Me 2 —C≡C—(CH2)4-(4-Me-cHx) H H
1-687 H H H Me 2 —C≡C—(CH2)4-(3-Et-cHx) H H
1-688 H H H Me 2 —C≡C—(CH2)4-(4-Et-cHx) H H
1-689 H H H Me 2 —C≡C—(CH2)4-(3-Pr-cHx) H H
1-690 H H H Me 2 —C≡C—(CH2)4-(4-Pr-cHx) H H
1-691 H H H Me 2 —C≡C—(CH2)4—(4-iPr-cHx) H H
1-692 H H H Me 2 —C≡C—(CH2)4-(3-Bu-cHx) H H
1-693 H H H Me 2 —C≡C—(CH2)4-(4-Bu-cHx) H H
1-694 H H H Me 2 —C≡C—(CH2)4-(3-CF3-cHx) H H
1-695 H H H Me 2 —C≡C—(CH2)4-(4-CF3-cHx) H H
1-696 H H H Me 2 —C≡C—(CH2)4-(3-MeO-cHx) H H
1-697 H H H Me 2 —C≡C—(CH2)4—(4-MeO-cHx) H H
1-698 H H H Me 2 —C≡C—(CH2)4-(3-EtO-cHx) H H
1-699 H H H Me 2 —C≡C—(CH2)4-(4-EtO-cHx) H H
1-700 H H H Me 2 —C≡C—(CH2)4-(3-PrO-cHx) H H
1-701 H H H Me 2 —C≡C—(CH2)4-(4-PrO-cHx) H H
1-702 H H H Me 2 —C≡C—(CH2)4-(3-iPrO-cHx) H H
1-703 H H H Me 2 —C≡C—(CH2)4-(4-iPrO-cHx) H H
1-704 H H H Me 2 —C≡C—(CH2)4-[3-(2-Et—PrO)-cHx] H H
1-705 H H H Me 2 —C≡C—(CH2)4-[4-(2—Et—PrO)-cHx] H H
1-706 H H H Me 2 —C≡C—(CH2)4-(3-iBuO-cHx) H H
1-707 H H H Me 2 —C≡C—(CH2)4-(4-iBuO-cHx) H H
1-708 H H H Me 2 —C≡C—(CH2)4-(3-MeS-cHx) H H
1-709 H H H Me 2 —C≡C—(CH2)4-(4-MeS-cHx) H H
1-710 H H H Me 2 —C≡C—(CH2)4-(3-EtS-cHx) H H
1-711 H H H Me 2 —C≡C—(CH2)4-(4-EtS-cHx) H H
1-712 H H H Me 2 —C≡C—(CH2)4-(3-PrS-cHx) H H
1-713 H H H Me 2 —C≡C—(CH2)4-(4-PrS-cHx) H H
1-714 H H H Me 2 —C≡C—(CH2)4-(3-iPrS-cHx) H H
1-715 H H H Me 2 —C≡C—(CH2)4-(4-iPrS-cHx) H H
1-716 H H H Me 2 —C≡C—(CH2)4-[3-(2-Et—PrS)-cHx] H H
1-717 H H H Me 2 —C≡C—(CH2)4-[4-(2-Et—PrS)-cHx] H H
1-718 H H H Me 2 —C≡C—(CH2)4-(3-iBuS-cHx) H H
1-719 H H H Me 2 —C≡C—(CH2)4-(4-iBuS-cHx) H H
1-720 H H H Me 2 —C≡C—(CH2)4-(3-cHx-cHx) H H
1-721 H H H Me 2 —C≡C—(CH2)4-(4-cHx-cHx) H H
1-722 H H H Me 2 —C≡C—(CH2)4-(3-Ph-cHx) H H
1-723 H H H Me 2 —C≡C—(CH2)4-(4-Ph-cHx) H H
1-724 H H H Me 2 —C≡C—(CH2)4-(2,4-diMe-cHx) H H
1-725 H H H Me 2 —C≡C—(CH2)4-(3,4-diMe-cHx) H H
1-726 H H H Me 2 —C≡C-(CH2)4-(3,5-diMe-cHx) H H
1-727 H H H Me 2 —C≡C—(CH2)4—Ph H H
1-728 H H H Me 2 —C≡C—(CH2)4—Ph Me H
1-729 H H H Me 2 —C≡C—(CH2)4—Ph H Me
1-730 H H H Me 2 —C≡C—(CH2)4—Ph F H
1-731 H H H Me 2 —C≡C—(CH2)4—Ph H F
1-732 H H H Me 2 —C≡C—(CH2)4-(3-F—Ph) H H
1-733 H H H Me 2 —C≡C—(CH2)4-(4-F—Ph) H H
1-734 H H H Me 2 —C≡C—(CH2)4-(4-Cl—Ph) H H
1-735 H H H Me 2 —C≡C—(CH2)4-(4-Br—Ph) H H
1-736 H H H Me 2 —C≡C—(CH2)4-(3-Me—Ph) H H
1-737 H H H Me 2 —C≡C—(CH2)4-(4-Me—Ph) H H
1-738 H H H Me 2 —C≡C—(CH2)4-(3-Et—Ph) H H
1-739 H H H Me 2 —C≡C—(CH2)4—(4-Et—Ph) H H
1-740 H H H Me 2 —C≡C—(CH2)4-(3-Pr—Ph) H H
1-741 H H H Me 2 —C≡C—(CH2)4-(4-Pr—Ph) H H
1-742 H H H Me 2 —C≡C—(CH2)4-(3-iPr—Ph) H H
1-743 H H H Me 2 —C≡C—(CH2)4-(4-iPr—Ph) H H
1-744 H H H Me 2 —C≡C—(CH2)4-(3-Bu—Ph) H H
1-745 H H H Me 2 —C≡C—(CH2)4-(4-Bu—Ph) H H
1-746 H H H Me 2 —C≡C—(CH2)4-(3-CF3—Ph) H H
1-747 H H H Me 2 —C≡C—(CH2)4-(4-CF3—Ph) H H
1-748 H H H Me 2 —C≡C—(CH2)4-(3-MeO—Ph) H H
1-749 H H H Me 2 —C≡C—(CH2)4-(4-MeO—Ph) H H
1-750 H H H Me 2 —C≡C—(CH2)4-(3-EtO—Ph) H H
1-751 H H H Me 2 —C≡C—(CH2)4-(4-EtO—Ph) H H
1-752 H H H Me 2 —C≡C—(CH2)4-(3-PrO—Ph) H H
1-753 H H H Me 2 —C≡C—(CH2)4-(4-PrO—Ph) H H
1-754 H H H Me 2 —C≡C—(CH2)4-(3-iPrO—Ph) H H
1-755 H H H Me 2 —C≡C—(CH2)4-(4-iPrO—Ph) H H
1-756 H H H Me 2 —C≡C—(CH2)4-[3-(2-Et—PrO)—Ph] H H
1-757 H H H Me 2 —C≡C—(CH2)4-[4-(2-Et—PrO)—Ph] H H
1-758 H H H Me 2 —C≡C—(CH2)4-(3-iBuO—Ph) H H
1-759 H H H Me 2 —C≡C—(CH2)4-(4-iBuO—Ph) H H
1-760 H H H Me 2 —C≡C—(CH2)4-(3-MeS—Ph) H H
1-761 H H H Me 2 —C≡C—(CH2)4-(4-MeS—Ph) H H
1-762 H H H Me 2 —C≡C—(CH2)4-(3-EtS—Ph) H H
1-763 H H H Me 2 —C≡C—(CH2)4-(4-EtS—Ph) H H
1-764 H H H Me 2 —C≡C—(CH2)4-(3-PrS—Ph) H H
1-765 H H H Me 2 —C≡C—(CH2)4-(4-PrS—Ph) H H
1-766 H H H Me 2 —C≡C—(CH2)4-(3-iPrS—Ph) H H
1-767 H H H Me 2 —C≡C—(CH2)4-(4-iPrS—Ph) H H
1-768 H H H Me 2 —C≡C—(CH2)4-[3-(2-Et—PrS)—Ph] H H
1-769 H H H Me 2 —C≡C—(CH2)4-[4-(2-Et—PrS)—Ph] H H
1-770 H H H Me 2 —C≡C—(CH2)4-(3-iBuS—Ph) H H
1-771 H H H Me 2 —C≡C—(CH2)4-(4-iBuS—Ph) H H
1-772 H H H Me 2 —C≡C—(CH2)4-(3-cHx-Ph) H H
1-773 H H H Me 2 —C≡C—(CH2)4-(4-cHx-Ph) H H
1-774 H H H Me 2 —C≡C—(CH2)4-(3-Ph—Ph) H H
1-775 H H H Me 2 —C≡C—(CH2)4-(4-Ph—Ph) H H
1-776 H H H Me 2 —C≡C—(CH2)4-(2,4-diMe—Ph) H H
1-777 H H H Me 2 —C≡C—(CH2)4-(3,4-diMe—Ph) H H
1-778 H H H Me 2 —C≡C—(CH2)4-(3,5-diMe—Ph) H H
1-779 H H H Me 2 —C≡C—(CH2)4-Np(1) H H
1-780 H H H Me 2 —C≡C—(CH2)4-Np(2) H H
1-781 H H H Me 2 —C≡C—(CH2)5-cHx H H
1-782 H H H Me 2 —C≡C—(CH2)5-(4-F-cHx) H H
1-783 H H H Me 2 —C≡C—(CH2)5-(4-Me-cHx) H H
1-784 H H H Me 2 —C≡C—(CH2)5-(4-Et-cHx) H H
1-785 H H H Me 2 —C≡C—(CH2)5-(4-CF3-cHx) H H
1-786 H H H Me 2 —C≡C—(CH2)5-(4-MeO-cHx) H H
1-787 H H H Me 2 —C≡C—(CH2)5-(4-EtO-cHx) H H
1-788 H H H Me 2 —C≡C—(CH2)5-(4-MeS-cHx) H H
1-789 H H H Me 2 —C≡C—(CH2)5-(4-cHx-cHx) H H
1-790 H H H Me 2 —C≡C—(CH2)5-(4-Ph-cHx) H H
1-791 H H H Me 2 —C≡C—(CH2)5—Ph H H
1-792 H H H Me 2 —C≡C—(CH2)5-(4-F—Ph) H H
1-793 H H H Me 2 —C≡C—(CH2)5-(4-Me—Ph) H H
1-794 H H H Me 2 —C≡C—(CH2)5-(4-Et—Ph) H H
1-795 H H H Me 2 —C≡C—(CH2)5-(4-CF3—Ph) H H
1-796 H H H Me 2 —C≡C—(CH2)5-(4-MeO—Ph) H H
1-797 H H H Me 2 —C≡C—(CH2)5-(4-EtO—Ph) H H
1-798 H H H Me 2 —C≡C—(CH2)5-(4-MeS—Ph) H H
1-799 H H H Me 2 —C≡C—(CH2)5-(4-cHx-Ph) H H
1-800 H H H Me 2 —C≡C—(CH2)5-(4-Ph—Ph) H H
1-801 H H H Me 2 —C≡C—(CH2)6-cHx H H
1-802 H H H Me 2 —C≡C—(CH2)6-(4-F-cHx) H H
1-803 H H H Me 2 —C≡C—(CH2)6-(4-Me-cHx) H H
1-804 H H H Me 2 —C≡C—(CH2)6-(4-Et-cHx) H H
1-805 H H H Me 2 —C≡C—(CH2)6-(4-CF3-cHx) H H
1-806 H H H Me 2 —C≡C—(CH2)6-(4-MeO-cHx) H H
1-807 H H H Me 2 —C≡C—(CH2)6-(4-EtO-cHx) H H
1-808 H H H Me 2 —C≡C—(CH2)6-(4-MeS-cHx) H H
1-809 H H H Me 2 —C≡C—(CH2)6-(4-cHx-cHx) H H
1-810 H H H Me 2 —C≡C—(CH2)6-(4-Ph-cHx) H H
1-811 H H H Me 2 —C≡C—(CH2)6—Ph H H
1-812 H H H Me 2 —C≡C—(CH2)6-(4-F—Ph) H H
1-813 H H H Me 2 —C≡C—(CH2)6-(4-Me—Ph) H H
1-814 H H H Me 2 —C≡C—(CH2)6-(4-Et—Ph) H H
1-815 H H H Me 2 —C≡C—(CH2)6-(4-CF3—Ph) H H
1-816 H H H Me 2 —C≡C—(CH2)6-(4-MeO—Ph) H H
1-817 H H H Me 2 —C≡C—(CH2)6-(4-EtO—Ph) H H
1-818 H H H Me 2 —C≡C—(CH2)6-(4-MeS—Ph) H H
1-819 H H H Me 2 —C≡C—(CH2)6-(4-cHx-Ph) H H
1-820 H H H Me 2 —C≡C—(CH2)6-(4-Ph—Ph) H H
1-821 H H H Me 2 —C≡C—CH2≡O-cHx H H
1-822 H H H Me 2 —C≡C—CH2—O-(4-F—cHx) H H
1-823 H H H Me 2 —C≡C—CH2—O-(4-Me-cHx) H H
1-824 H H H Me 2 —C≡C—CH2—O-(4-Et-cHx) H H
1-825 H H H Me 2 —C≡C—CH2—O- (4-CF3-cHx) H H
1-826 H H H Me 2 —C≡C—CH2—O-(4-MeO-cHx) H H
1-827 H H H Me 2 —C≡C—CH2—O-(4-EtO-cHx) H H
1-828 H H H Me 2 —C≡C—CH2—O-(4-MeS-cHx) H H
1-829 H H H Me 2 —C≡C—CH2—O-(4-cHx-cHx) H H
1-830 H H H Me 2 —C≡C—CH2-O-(4-Ph-cHx) H H
1-831 H H H Me 2 —C≡C—CH2—O—Ph H H
1-832 H H H Me 2 —C≡C—CH2—O-(4-F—Ph) H H
1-833 H H H Me 2 —C≡C—CH2—O-(4-Me—Ph) H H
1-834 H H H Me 2 —C≡C—CH2—O-(4-Et—Ph) H H
1-835 H H H Me 2 —C≡C—CH2—O-(4-CF3—Ph) H H
1-836 H H H Me 2 —C≡C—CH2—O-(4-MeO—Ph) H H
1-837 H H H Me 2 —C≡C—CH2—O-(4-EtO—Ph) H H
1-838 H H H Me 2 —C≡C—CH2—O-(4-MeS—Ph) H H
1-839 H H H Me 2 —C≡C—CH2—O-(4-cHx-Ph) H H
1-840 H H H Me 2 —C≡C—CH2—O-(4-Ph—Ph) H H
1-841 H H H Me 2 —C≡C—(CH2)2O-cPn H H
1-842 H H H Me 2 —C≡C—(CH2)2O-cHx H H
1-843 H H H Me 2 —C≡C—(CH2)2O-cHx Me H
1-844 H H H Me 2 —C≡C—(CH2)2O-cHx H Me
1-845 H H H Me 2 —C≡C—(CH2)2O-cHx F H
1-846 H H H Me 2 —C≡C—(CH2)2O-cHx H F
1-847 H H H Me 2 —C≡C—(CH2)2O-(3-F-cHx) H H
1-848 H H H Me 2 —C≡C—(CH2)2O-(4-F-cHx) H H
1-849 H H H Me 2 —C≡C—(CH2)2O-(4-Cl-cHx) H H
1-850 H H H Me 2 —C≡C—(CH2)2O-(4-Br-cHx) H H
1-851 H H H Me 2 —C≡C—(CH2)2O-(3-Me-cHx) H H
1-852 H H H Me 2 —C≡C—(CH2)2O-(4-Me-cHx) H H
1-853 H H H Me 2 —C≡C—(CH2)2O-(3-Et-cHx) H H
1-854 H H H Me 2 —C≡C—(CH2)2O-(4-Et-cHx) H H
1-855 H H H Me 2 —C≡C—(CH2)2O-(3-Pr-cHx) H H
1-856 H H H Me 2 —C≡C—(CH2)2O-(4-Pr-cHx) H H
1-857 H H H Me 2 —C≡C—(CH2)2O-(4-iPr-cHx) H H
1-858 H H H Me 2 —C≡C—(CH2)2O-(3-Bu-cHx) H H
1-859 H H H Me 2 —C≡C—(CH2)2O-(4-Bu-cHx) H H
1-860 H H H Me 2 —C≡C—(CH2)2O-(3-CF3-cHx) H H
1-861 H H H Me 2 —C≡C—(CH2)2O-(4-CF3-cHx) H H
1-862 H H H Me 2 —C≡C—(CH2)2O-(3-MeO-cHx) H H
1-863 H H H Me 2 —C≡C—(CH2)2O-(4-MeO-cHx) H H
1-864 H H H Me 2 —C≡C—(CH2)2O-(3-EtO-cHx) H H
1-865 H H H Me 2 —C≡C—(CH2)2O-(4-EtO-cHx) H H
1-866 H H H Me 2 —C≡C—(CH2)2O-(3-PrO-cHx) H H
1-867 H H H Me 2 —C≡C—(CH2)2O-(4-PrO-cHx) H H
1-868 H H H Me 2 —C≡C—(CH2)2O-(3-iPrO-cHx) H H
1-869 H H H Me 2 —C≡C—(CH2)2O-(4-iPrO-cHx) H H
1-870 H H H Me 2 —C≡C—(CH2)2O-[3-(2-Et—PrO)-cHx] H H
1-871 H H H Me 2 —C≡C—(CH2)2O-[4-(2-Et—Pro)-cHx] H H
1-872 H H H Me 2 —C≡C—(CH2)2O-(3-iBuO-cHx) H H
1-873 H H H Me 2 —C≡C—(CH2)2O-(4-iBuO-cHx) H H
1-874 H H H Me 2 —C≡C—(CH2)2O-(3-MeS-cHx) H H
1-875 H H H Me 2 —C≡C—(CH2)2O-(4-MeS-cHx) H H
1-876 H H H Me 2 —C≡C—(CH2)2O-(3-EtS-cHx) H H
1-877 H H H Me 2 —C≡C—(CH2)2O-(4-EtS-cHx) H H
1-878 H H H Me 2 —C≡C—(CH2)2O-(3-PrS-cHx) H H
1-879 H H H Me 2 —C≡C—(CH2)2O-(4-PrS-cHx) H H
1-880 H H H Me 2 —C≡C—(CH2)2O-(3-iPrS-cHx) H H
1-881 H H H Me 2 —C≡C—(CH2)2O-(4-iPrS-cHx) H H
1-882 H H H Me 2 —C≡C—(CH2)2O-[3-(2-Et—PrS)-cHx] H H
1-883 H H H Me 2 —C≡C—(CH2)2O-[4-(2-Et—PrS)-cHx] H H
1-884 H H H Me 2 —C≡C—(CH2)2O-(3-iBuS-cHx) H H
1-885 H H H Me 2 —C≡C—(CH2)2O-(4-iBuS-cHx) H H
1-886 H H H Me 2 —C≡C—(CH2)2O-(3-cHx-cHx) H H
1-887 H H H Me 2 —C≡C—(CH2)2O-(4-cHx-cHx) H H
1-888 H H H Me 2 —C≡C—(CH2)2O-(3-Ph-cHx) H H
1-889 H H H Me 2 —C≡C—(CH2)2O-(4-Ph-cHx) H H
1-890 R H H Me 2 —C≡C—(CH2)2O-(2,4-diMe-cHx) H H
1-891 H H H Me 2 —C≡C—(CH2)2O-(3,4-diMe-cHx) H H
1-892 H H H Me 2 —C≡C—(CH2)2O-(3,5-diMe-cHx) H H
1-893 H H H Me 2 —C≡C—(CH2)2O—Ph H H
1-894 H H H Me 2 —C≡C—(CH2)2O—Ph Me H
1-895 H H H Me 2 —C≡C—(CH2)2O—Ph H Me
1-896 H H H Me 2 —C≡C—(CH2)2O—Ph F H
1-897 H H H Me 2 —C≡C—(CH2)2O—Ph H F
1-898 H H H Me 2 —C≡C—(CH2)2O-(3-F—Ph) H H
1-899 H H H Me 2 —C≡C—(CH2)2O-(4-F—Ph) H H
1-900 H H H Me 2 —C≡C—(CH2)2O-(4-Cl—Ph) H H
1-901 H H H Me 2 —C≡C—(CH2)2O-(4-Br—Ph) H H
1-902 H H H Me 2 —C≡C—(CH2)2O-(3—Me—Ph) H H
1-903 H H H Me 2 —C≡C—(CH2)2O-(4-Me—Ph) H H
1-904 H H H Me 2 —C≡C—(CH2)2O-(3-Et—Ph) H H
1-905 H H H Me 2 —C≡C—(CH2)2O-(4-Et—Ph) H H
1-906 H H H Me 2 —C≡C—(CH2)2O-(3-Pr—Ph) H H
1-907 H H H Me 2 —C≡C—(CH2)2O-(4-Pr—Ph) H H
1-908 H H H Me 2 —C≡C—(CH2)2O-(3-iPr—Ph) H H
1-909 H H H Me 2 —C≡C—(CH2)2O-(4-iPr—Ph) H H
1-910 H H H Me 2 —C≡C—(CH2)2O-(3-Bu—Ph) H H
1-921 H H H Me 2 —C≡C—(CH2)2O-(4-Bu-Ph) H H
1-912 H H H Me 2 —C≡C—(CH2)2O-(3-CF3—Ph) H H
1-913 H H H Me 2 —C≡C—(CH2)2O-(4-CF3—Ph) H H
1-914 H H H Me 2 —C≡C—(CH2)2O-(3-MeO—Ph) H H
1-915 H H H Me 2 —C≡C—(CH2)2O-(4-MeO—Ph) H H
1-916 H H H Me 2 —C≡C—(CH2)2O-(3-EtO—Ph) H H
1-917 H H H Me 2 —C≡C—(CH2)2O-(4-EtO—Ph) H H
1-918 H H H Me 2 —C≡C—(CH2)2O-(3-PrO—Ph) H H
1-919 H H H Me 2 —C≡C—(CH2)2O-(4-PrO—Ph) H H
1-920 H H H Me 2 —C≡C—(CH2)2O-(3-iPrO—Ph) H H
1-921 H H H Me 2 —C≡C—(CH2)2O-(4-iPrO—Ph) H H
1-922 H H H Me 2 —C≡C—(CH2)2O-[3-(2-Et—PrO)—Ph] H H
1-923 H H H Me 2 —C≡C—(CH2)2O-[4-(2-Et—PrO)—Ph] H H
1-924 H H H Me 2 —C≡C—(CH2)2O-(3-iBuO—Ph) H H
1-925 H H H Me 2 —C≡C—(CH2)2O-(4-iBuO—Ph) H H
1-926 H H H Me 2 —C≡C—(CH2)2O-(3-MeS—Ph) H H
1-927 H H H Me 2 —C≡C—(CH2)2O-(4-MeS—Ph) H H
1-928 H H H Me 2 —C≡C—(CH2)2O-(3-EtS—Ph) H H
1-929 H H H Me 2 —C≡C—(CH2)2O-(4-EtS—Ph) H H
1-930 H H H Me 2 —C≡C—(CH2)2O-(3-PrS—Ph) H H
1-931 H H H Me 2 —C≡C—(CH2)2O-(4-PrS—Ph) H H
1-932 H H H Me 2 —C≡C—(CH2)2O-(3-iPrS—Ph) H H
1-933 H H H Me 2 —C≡C—(CH2)2O-(4-iPrS—Ph) H H
1-934 H H H Me 2 —C≡C—(CH2)2O-[3-(2-Et—PrS)—Ph] H H
1-935 H H H Me 2 —C≡C—(CH2)2O-[4-(2-Et—PrS)—Ph] H H
1-936 H H H Me 2 —C≡C—(CH2)2O-(3-iBuS—Ph) H H
1-937 H H H Me 2 —C≡C—(CH2)2O-(4-iBuS—Ph) H H
1-938 H H H Me 2 —C≡C—(CH2)2O-(3-cHx-Ph) H H
1-939 H H H Me 2 —C≡C—(CH2)2O-(4-cHx-Ph) H H
1-940 H H H Me 2 —C≡C—(CH2)2O-(3-Ph—Ph) H H
1-941 H H H Me 2 —C≡C—(CH2)2O-(4-Ph—Ph) H H
1-942 H H H Me 2 —C≡C—(CH2)2O-(2,4-diMe—Ph) H H
1-943 H H H Me 2 —C≡C—(CH2)2O-(3,4-diMe—Ph) H H
1-944 H H H Me 2 —C≡C—(CH2)2O-(3,5-diMe—Ph) H H
1-945 H H H Me 2 —C≡C—(CH2)3O-cHx H H
1-946 H H H Me 2 —C≡C—(CH2)3O—Ph H H
1-947 H H H Me 2 —C≡C—(CH2)4O-cHx H H
1-948 H H H Me 2 —C≡C—(CH2)4O—Ph H H
1-949 H H H Me 2 —C≡C—CH2—OCH2-cHx H H
1-950 H H H Me 2 —C≡C—CH2—OCH2-(4-F-cHx) H H
1-951 H H H Me 2 —C≡C—CH2—OCH2-(4-Me-cHx) H H
1-952 H H H Me 2 —C≡C—CH2—OCH2-(4-Et-cHx) H H
1-953 H H H Me 2 —C≡C—CH2—OCH2-(4-CF3-cHx) H H
1-954 H H H Me 2 —C≡C—CH2—OCH2-(4-MeO-cHx) H H
1-955 H H H Me 2 —C≡C—CH2—OCH2-(4-EtO-cHx) H H
1-956 H H H Me 2 —C≡C—CH2—OCH2-(4-MeS-cHx) H H
1-957 H H H Me 2 —C≡C—CH2—OCH2-(4-cHx-cHx) H H
1-958 H H H Me 2 —C≡C—CH2—OCH2-(4-Ph-cHx) H H
1-959 H H H Me 2 —C≡C—CH2—OCH2—Ph H H
1-960 H H H Me 2 —C≡C—CH2—OCH2-(4-F—Ph) H H
1-961 H H H Me 2 —C≡C—CH2—OCH2-(4-Me—Ph) H H
1-962 H H H Me 2 —C≡C—CH2—OCH2-(4-Et—Ph) H H
1-963 H H H Me 2 —C≡C—CH2—OCH2-(4-CF3—Ph) H H
1-964 H H H Me 2 —C≡C—CH2—OCH2-(4-MeO—Ph) H H
1-965 H H H Me 2 —C≡C—CH2—OCH2-(4-EtO—Ph) H H
1-966 H H H Me 2 —C≡C—CH2—OCH2-(4-MeS—Ph) H H
1-967 H H H Me 2 —C≡C—CH2—OCH2-(4-cHx-Ph) H H
1-968 H H H Me 2 —C≡C—CH2—OCH2-(4-Ph—Ph) H H
1-969 H H H Me 2 —C≡C—(CH2)2—OCH2-cPn H H
1-970 H H H Me 2 —C≡C—(CH2)2—OCH2-cHx H H
1-971 H H H Me 2 —C≡C—(CH2)2—OCH2-cHx Me H
1-972 H H H Me 2 —C≡C—(CH2) 2—OCH2-cHx H Me
1-973 H H H Me 2 —C≡C—(CH2)2—OCH2-cHx F H
1-974 H H H Me 2 —C≡C—(CH2)2—OCH2-cHx H F
1-975 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-F-cHx) H H
1-976 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-F-cHx) H H
1-977 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Cl-cHx) H H
1-978 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Br-cHx) H H
1-979 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Me-cHx) H H
1-980 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Me-cHx) H H
1-981 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Et-cHx) H H
1-982 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Et-cHx) H H
1-983 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Pr-cHx) H H
1-984 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Pr-cHx) H H
1-985 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iPr-cHx) H H
1-986 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Bu-cHx) H H
1-987 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Bu-cHx) H H
1-988 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-CF3-cHx) H H
1-989 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-CF3-cHx) H H
1-990 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-MeO-cHx) H H
1-991 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-MeO-cHx) H H
1-992 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-EtO-cHx) H H
1-993 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-EtO-cHx) H H
1-994 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-PrO-cHx) H H
1-995 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-PrO-cHx) H H
1-996 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iPrO-cHx) H H
1-997 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iPrO-cHx) H H
1-998 H H H Me 2 —C≡C—(CH2)2—OCH2-[3-(2-Et—PrO)cHx] H H
1-999 H H H Me 2 —C≡C—(CH2)2—OCH2-[4-(2-Et—PrO)cHx] H H
1-1000 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iBuO—cHx) H H
1-1001 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iBuO-cHx) H H
1-1002 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-MeS-cHx) H H
1-1003 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-MeS-cHx) H H
1-2004 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-EtS-cHx) H H
1-2005 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-EtS-cHx) H H
1-2006 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-PrS-cHx) H H
1-2007 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-PrS-cHx) H H
1-2008 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iPrS-cHx) H H
1-2009 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iPrS-cHx) H H
1-1010 H H H Me 2 —C≡C—(CH2)2—OCH2-[3-(2-Et—PrS)cHx] H H
1-1011 H H H Me 2 —C≡C—(CH2)2—OCH2-[4-(2-Et—PrS)cHx] H H
1-1012 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iBuS-cHx) H H
1-1013 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iBuS-cHx) H H
1-1014 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-cHx-cHx) H H
1-1015 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-cHx-cHx) H H
1-1016 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Ph-cHx) H H
1-1017 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Ph-cHx) H H
1-1018 H H H Me 2 —C≡C—(CH2)2—OCH2-(2,4-diMe-cHx) H H
1-1019 H H H Me 2 —C≡C—(CH2)2—OCH2-(3,4-diMe-cHx) H H
1-1020 H H H Me 2 —C≡C—(CH2)2—OCH2-(3,5-diMe-cHx) H H
1-1021 H H H Me 2 —C≡C—(CH2)2—OCH2—Ph H H
1-1022 H H H Me 2 —C≡C—(CH2)2—OCH2—Ph Me H
1-1023 H H H Me 2 —C≡C—(CH2)2—OCH2—Ph H Me
1-1024 H H H Me 2 —C≡C—(CH2)2—OCH2—Ph F H
1-1025 H H H Me 2 —C≡C—(CH2)2—OCH2—Ph H F
1-1026 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-F—Ph) H H
1-1027 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-F—Ph) H H
1-1028 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Cl—Ph) H H
1-1029 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Br—Ph) H H
1-1030 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Me—Ph) H H
1-1031 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Me—Ph) H H
1-1032 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Et—Ph) H H
1-1033 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Et—Ph) H H
1-1034 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Pr—Ph) H H
1-1035 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Pr—Ph) H H
1-1036 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iPr—Ph) H H
1-1037 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iPr—Ph) H H
1-1038 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Bu—Ph) H H
1-1039 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Bu—Ph) H H
1-1040 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-CF3—Ph) H H
1-1041 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-CF3—Ph) H H
1-1042 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-MeO—Ph) H H
1-1043 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-MeO—Ph) H H
1-1044 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-EtO—Ph) H H
1-1045 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-EtO—Ph) H H
1-1046 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-PrO—Ph) H H
1-1047 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-PrO—Ph) H H
1-1048 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iPrO—Ph) H H
1-1049 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iPrO—Ph) H H
1-1050 H H H Me 2 —C≡C—(CH2)2—OCH2-[3-(2-Et—PrO)Ph] H H
1-1051 H H H Me 2 —C≡C—(CH2)2—OCH2-[4-(2-Et—PrO)Ph] H H
1-1052 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iBuO—Ph) H H
1-1053 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iBuO—Ph) H H
1-1054 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-MeS—Ph) H H
1-1055 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-MeS—Ph) H H
1-1056 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-EtS—Ph) H H
1-1057 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-EtS—Ph) H H
1-1058 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-PrS—Ph) H H
1-1059 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-PrS—Ph) H H
1-1060 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iPrS—Ph) H H
1-1061 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iPrS—Ph) H H
1-1062 H H H Me 2 —C≡C—(CH2)2—OCH2-[3-(2-Et—PrS)Ph] H H
1-1063 H H H Me 2 —C≡C—(CH2)2—OCH2-[4-(2-Et—PrS)Ph] H H
1-1064 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-iBuS—Ph) H H
1-1065 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-iBuS—Ph) H H
1-1066 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-cHx-Ph) H H
1-1067 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-cHx-Ph) H H
1-1068 H H H Me 2 —C≡C—(CH2)2—OCH2-(3-Ph—Ph) H H
1-1069 H H H Me 2 —C≡C—(CH2)2—OCH2-(4-Ph—Ph) H H
1-1070 H H H Me 2 —C≡C—(CH2)2—OCH2-(2,4-diMe—Ph) H H
1-1071 H H H Me 2 —C≡C—(CH2)2—OCH2-(3,4-diMe—Ph) H H
1-1072 H H H Me 2 —C≡C—(CH2)2—OCH2-(3,5-diMe—Ph) H H
1-1073 H H H Me 2 —C≡C—(CH2)3—OCH2-cHx H H
1-1074 H H H Me 2 —C≡C—(CH2)3—OCH2—Ph H H
1-1075 H H H Me 2 —C≡C—(CH2)4—OCH2-cHx H H
1-1076 H H H Me 2 —C≡C—(CH2)4—OCH2—Ph H H
1-1077 H H H Me 2 —CO—CH2-(4-cHx-Ph) H H
1-1078 H H H Me 2 —CO—CH2-(4-Ph—Ph) H H
1-1079 H H H Me 2 —CO—(CH2)2-cHx H H
1-1080 H H H Me 2 —CO—(CH2)2—Ph H H
1-1081 H H H Me 2 —CO—(CH2)3-cHx H H
1-1082 H H H Me 2 —CO—(CH2)3—Ph H H
1-1083 H H H Me 2 —CO—(CH2)4-cHx H H
1-1084 H H H Me 2 —CO—(CH2)4-(4-F-cHx) H H
1-1085 H H H Me 2 —CO—(CH2)4-(4-Me-cHx) H H
1-1086 H H H Me 2 —CO—(CH2)4-(4-Et-cHx) H H
1-1087 H H H Me 2 —CO—(CH2)4-(4-CF3-cHx) H H
1-1088 H H H Me 2 —CO—(CH2)4-(4-MeO-cHx) H H
1-1089 H H H Me 2 —CO—(CH2)4-(4-EtO-cHx) H H
1-1090 H H H Me 2 —CO—(CH2)4-(4-MeS-cHx) H H
1-1091 H H H Me 2 —CO—(CH2)4-(4-cHx-cHx) H H
1-1092 H H H Me 2 —CO—(CH2)4-(4-Ph-cHx) H H
1-1093 H H H Me 2 —CO—(CH2)4—Ph H H
1-1094 H H H Me 2 —CO—(CH2)4-(4-F—Ph) H H
1-1095 H H H Me 2 —CO—(CH2)4-(4-Me—Ph) H H
1-1096 H H H Me 2 —CO—(CH2)4-(4-Et—Ph) H H
1-1097 H H H Me 2 —CO—(CH2)4-(4-CF3—Ph) H H
1-1098 H H H Me 2 —CO—(CH2)4-(4-MeO—Ph) H H
1-1099 H H H Me 2 —CO—(CH2)4-(4-EtO—Ph) H H
1-1100 H H H Me 2 —CO—(CH2)4-(4-MeS—Ph) H H
1-1101 H H H Me 2 —CO—(CH2)4-(4-cHx-Ph) H H
1-1102 H H H Me 2 —CO—(CH2)4-(4-Ph—Ph) H H
1-1103 H H H Me 2 —CO—(CH2)5-cHx H H
1-1104 H H H Me 2 —CO—(CH2)5-(4-F-cHx) H H
1-1105 H H H Me 2 —CO—(CH2)5-(4-Me-cHx) H H
1-1106 H H H Me 2 —CO—(CH2)5-(4-Et-cHx) H H
1-1107 H H H Me 2 —CO—(CH2)5-(4-CF3-cHx) H H
1-1108 H H H Me 2 —CO—(CH2)5-(4-MeO-cHx) H H
1-1109 H H H Me 2 —CO—(CH2)5-(4-EtO-cHx) H H
1-1110 H H H Me 2 —CO—(CH2)5-(4-MeS-cHx) H H
1-1111 H H H Me 2 —CO—(CH2)5-(4-cHx-cHx) H H
1-1112 H H H Me 2 —CO—(CH2)5-(4-Ph-cHx) H H
1-1113 H H H Me 2 —CO—(CH2)5—Ph H H
1-1114 H H H Me 2 —CO—(CH2)5-(4-F—Ph) H H
1-1115 H H H Me 2 —CO—(CH2)5-(4-Me—Ph) H H
1-1116 H H H Me 2 —CO—(CH2)5-(4-Et—Ph) H H
1-1117 H H H Me 2 —CO—(CH2)5-(4-CF3—Ph) H H
1-1118 H H H Me 2 —CO—(CH2)5-(4-MeO—Ph) H H
1-1119 H H H Me 2 —CO—(CH2)5-(4-EtO—Ph) H H
1-1120 H H H Me 2 —CO—(CH2)5-(4-MeS—Ph) H H
1-1121 H H H Me 2 —CO—(CH2)5-(4-cHx-Ph) H H
1-1222 H H H Me 2 —CO—(CH2)5-(4-Ph—Ph) H H
1-1223 H H H Me 2 —CO—(CH2)6-cHx H H
1-1224 H H H Me 2 —CO—(CH2)6—Ph H H
1-1225 H H H Me 2 —CO—(CH2)7-cHx H H
1-1126 H H H Me 2 —CO—(CH2)7—Ph H H
1-1127 H H H Me 2 —CO—(CH2)2—O-cHx H H
1-1128 H H H Me 2 —CO—(CH2)2—O-(4-F-cHx) H H
1-1129 H H H Me 2 —CO—(CH2)2—O-(4-Me-cHx) H H
1-1130 H H H Me 2 —CO—(CH2)2—O-(4-Et-cHx) H H
1-1131 H H H Me 2 —CO—(CH2)2—O-(4-CF3-cHx) H H
1-1132 H H H Me 2 —CO—(CH2)2—O-(4-MeO-cHx) H H
1-1133 H H H Me 2 —CO—(CH2)2—O-(4-EtO-cHx) H H
1-1134 H H H Me 2 —CO—(CH2)2—O-(4-MeS-cHx) H H
1-1135 H H H Me 2 —CO—(CH2)2—O-(4-cHx-cHx) H H
1-1136 H H H Me 2 —CO—(CH2)2—O-(4-Ph-cHx) H H
1-1137 H H H Me 2 —CO—(CH2)2—O—Ph H H
1-1138 H H H Me 2 —CO—(CH2)2—O-(4-F—Ph) H H
1-1139 H H H Me 2 —CO—(CH2)2—O-(4-Me—Ph) H H
1-1140 H H H Me 2 —CO—(CH2)2—O-(4-Et—Ph) H H
1-1141 H H H Me 2 —CO—(CH2)2—O-(4-CF3—Ph) H H
1-1142 H H H Me 2 —CO—(CH2)2—O-(4-MeO—Ph) H H
1-1143 H H H Me 2 —CO—(CH2)2—O-(4-EtO—Ph) H H
1-1144 H H H Me 2 —CO—(CH2)2—O-(4-MeS—Ph) H H
1-1145 H H H Me 2 —CO—(CH2)2—O-(4-cHx-Ph) H H
1-1146 H H H Me 2 —CO—(CH2)2—O-(4-Ph—Ph) H H
1-1147 H H H Me 2 —CO—(CH2)3—O-cPn H H
1-1148 H H H Me 2 —CO—(CH2)3—O-cHx H H
1-1149 H H H Me 2 —CO—(CH2)3—O-cHx Me H
1-1150 H H H Me 2 —CO—(CH2)3—O-cHx H Me
1-1151 H H H Me 2 —CO—(CH2)3—O-cHx F H
1-1152 H H H Me 2 —CO—(CH2)3—O-cHx H F
1-1153 H H H Me 2 —CO—(CH2)3—O-(3-F-cHx) H H
1-1154 H H H Me 2 —CO—(CH2)3—O-(4-F-cHx) H H
1-1155 H H H Me 2 —CO—(CH2)3—O-(4-Cl-cHx) H H
1-1156 H H H Me 2 —CO—(CH2)3—O-(4-Br-cHx) H H
1-1157 H H H Me 2 —CO—(CH2)3—O-(3-Me-cHx) H H
1-1158 H H H Me 2 —CO—(CH2)3—O-(4-Me-cHx) H H
1-1159 H H H Me 2 —CO—(CH2)3—O-(3-Et-cHx) H H
1-1160 H H H Me 2 —CO—(CH2)3—O-(4-Et-cHx) H H
1-1161 H H H Me 2 —CO—(CH2)3—O-(3-Pr-cHx) H H
1-1162 H H H Me 2 —CO—(CH2)3—O-(4-Pr-cHx) H H
1-1163 H H H Me 2 —CO—(CH2)3—O-(4-iPr-cHx) H H
1-1164 H H H Me 2 —CO—(CH2)3—O-(3-Bu-cHx) H H
1-1165 H H H Me 2 —CO—(CH2)3—O-(4-Bu-cHx) H H
1-1166 H H H Me 2 —CO—(CH2)3—O-(3-CF3-cHx) H H
1-1167 H H H Me 2 —CO—(CH2)3—O-(4-CF3—cHx) H H
1-1168 H H H Me 2 —CO—(CH2)3—O-(3-MeO-cHx) H H
1-1169 H H H Me 2 —CO—(CH2)3—O-(4-MeO-cHx) H H
1-1170 H H H Me 2 —CO—(CH2)3—O-(3-EtO-cHx) H H
1-1171 H H H Me 2 —CO—(CH2)3—O-(4-EtO-cHx) H H
1-1172 H H H Me 2 —CO—(CH2)3—O-(3-PrO-cHx) H H
1-1173 H H H Me 2 —CO—(CH2)3—O-(4-PrO-cHx) H H
1-1174 H H H Me 2 —CO—(CH2)3—O-(3-iPrO-cHx) H H
1-1175 H H H Me 2 —CO—(CH2)3—O-(4-iPrO-cHx) H H
1-1176 H H H Me 2 —CO—(CH2)3—O-[3-(2-Et—PrO)cHx] H H
1-1177 H H H Me 2 —CO—(CH2)3—O-[4-(2-Et—PrO)cHx] H H
1-1178 H H H Me 2 —CO—(CH2)3—O-(3-iBuO-cHx) H H
1-1179 H H H Me 2 —CO—(CH2)3—O-(4-iBuO-cHx) H H
1-1180 H H H Me 2 —CO—(CH2)3—O-(3-MeS-cHx) H H
1-1181 H H H Me 2 —CO—(CH2)3—O-(4-MeS-cHx) H H
1-1182 H H H Me 2 —CO—(CH2)3—O-(3-EtS-cHx) H H
1-1183 H H H Me 2 —CO—(CH2)3—O-(4-EtS-cHx) H H
1-1184 H H H Me 2 —CO—(CH2)3—O-(3-PrS-cHx) H H
1-1185 H H H Me 2 —CO—(CH2)3—O-(4-PrS-cHx) H H
1-1186 H H H Me 2 —CO—(CH2)3—O-(3-iPrS-cHx) H H
1-1187 H H H Me 2 —CO—(CH2)3—O-(4-iPrS-cHx) H H
1-1188 H H H Me 2 —CO—(CH2)3—O-[3-(2-Et—PrS)cHx] H H
1-1189 H H H Me 2 —CO—(CH2)3—O-[4-(2-Et—PrS)cHx] H H
1-1190 H H H Me 2 —CO—(CH2)3—O-(3-iBuS-cHx) H H
1-1191 H H H Me 2 —CO—(CH2)3—O-(4-iBuS-cHx) H H
1-1192 H H H Me 2 —CO—(CH2)3—O-(3-cHx-cHx) H H
1-1193 H H H Me 2 —CO—(CH2)3—O-(4-cHx-cHx) H H
1-1194 H H H Me 2 —CO—(CH2)3—O-(3-Ph-cHx) H H
1-1195 H H H Me 2 —CO—(CH2)3—O-(4-Ph-cHx) H H
1-1196 H H H Me 2 —CO—(CH2)3—O-(2,4-diMe-cHx) H H
1-1197 H H H Me 2 —CO—(CH2)3—O-(3,4-diMe-cHx) H H
1-1198 H H H Me 2 —CO—(CH2)3—O-(3,5-diMe-cHx) H H
1-1199 H H H Me 2 —CO—(CH2)3—O—Ph H H
1-1200 H H H Me 2 —CO—(CH2)3—O—Ph Me H
1-1201 H H H Me 2 —CO—(CH2)3—O—Ph H Me
1-1202 H H H Me 2 —CO—(CH2)3—O—Ph F H
1-1203 H H H Me 2 —CO—(CH2)3—O—Ph H F
1-1204 H H H Me 2 —CO—(CH2)3—O-(3-F—Ph) H H
1-1205 H H H Me 2 —CO—(CH2)3—O-(4-F—Ph) H H
1-1206 H H H Me 2 —CO—(CH2)3—O-(4-Cl—Ph) H H
1-1207 H H H Me 2 —CO—(CH2)3—O-(4-Br—Ph) H H
1-1208 H H H Me 2 —CO—(CH2)3—O-(3-Me—Ph) H H
1-1209 H H H Me 2 —CO—(CH2)3—O-(4-Me—Ph) H H
1-1210 H H H Me 2 —CO—(CH2)3—O-(3-Et—Ph) H H
1-1211 H H H Me 2 —CO—(CH2)3—O-(4-Et—Ph) H H
1-1212 H H H Me 2 —CO—(CH2)3—O-(3-Pr—Ph) H H
1-1213 H H H Me 2 —CO—(CH2)3—O-(4-Pr—Ph) H H
1-1214 H H H Me 2 —CO—(CH2)3—O-(3-iPr—Ph) H H
1-1215 H H H Me 2 —CO—(CH2)3—O-(4-iPr—Ph) H H
1-1216 H H H Me 2 —CO—(CH2)3—O-(3-Bu—Ph) H H
1-1217 H H H Me 2 —CO—(CH2)3—O-(4-Bu—Ph) H H
1-1218 H H H Me 2 —CO—(CH2)3—O-(3-CF3—Ph) H H
1-1219 H H H Me 2 —CO—(CH2)3—O-(4-CF3—Ph) H H
1-1220 H H H Me 2 —CO—(CH2)3—O-(3-MeO—Ph) H H
1-1221 H H H Me 2 —CO—(CH2)3—O-(4-MeO—Ph) H H
1-1222 H H H Me 2 —CO—(CH2)3—O-(3-EtO—Ph) H H
1-1223 H H H Me 2 —CO—(CH2)3—O-(4-EtO—Ph) H H
1-1224 H H H Me 2 —CO—(CH2)3—O-(3-PrO—Ph) H H
1-1225 H H H Me 2 —CO—(CH2)3—O-(4-PrO—Ph) H H
1-1226 H H H Me 2 —CO—(CH2)3—O-(3-iPrO—Ph) H H
1-1227 H H H Me 2 —CO—(CH2)3—O-(4-iPrO—Ph) H H
1-1228 H H H Me 2 —CO—(CH2)3—O-[3-(2-Et—PrO)—Ph] H H
1-1229 H H H Me 2 —CO—(CH2)3—O-[4-(2-Et—PrO)—Ph] H H
1-1230 H H H Me 2 —CO—(CH2)3—O-(3-iBuO—Ph) H H
1-1231 H H H Me 2 —CO—(CH2)3—O-(4-iBuO—Ph) H H
1-1232 H H H Me 2 —CO—(CH2)3—O-(3-MeS—Ph) H H
1-1233 H H H Me 2 —CO—(CH2)3—O-(4-MeS—Ph) H H
1-1234 H H H Me 2 —CO—(CH2)3—O-(3-EtS—Ph) H H
1-1235 H H H Me 2 —CO—(CH2)3—O-(4-EtS—Ph) H H
1-1236 H H H Me 2 —CO—(CH2)3—O-(3-PrS—Ph) H H
1-1237 H H H Me 2 —CO—(CH2)3—O-(4-PrS—Ph) H H
1-1238 H H H Me 2 —CO—(CH2)3—O-(3-iPrS—Ph) H H
1-1239 H H H Me 2 —CO—(CH2)3—O-(4-iPrS—Ph) H H
1-1240 H H H Me 2 —CO—(CH2)3—O-[3-(2-Et—PrS)—Ph] H H
1-1241 H H H Me 2 —CO—(CH2)3—O-[4-(2-Et—PrS)—Ph] H H
1-1242 H H H Me 2 —CO—(CH2)3—O-(3-iBuS—Ph) H H
1-1243 H H H Me 2 —CO—(CH2)3—O-(4-iBuS—Ph) H H
1-1244 H H H Me 2 —CO—(CH2)3—O-(3-cHx-Ph) H H
1-1245 H H H Me 2 —CO—(CH2)3—O-(4-cHx-Ph) H H
1-1246 H H H Me 2 —CO—(CH2)3—O-(3-Ph—Ph) H H
1-1247 H H H Me 2 —CO—(CH2)3-O-(4-Ph—Ph) H H
1-1248 H H H Me 2 —CO—(CH2)3—O-(2,4-diMe—Ph) H H
1-1249 H H H Me 2 —CO—(CH2)3—O-(3,4-diMe—Ph) H H
1-1250 H H H Me 2 —CO—(CH2)3—O-(3,5-diMe—Ph) H H
1-1251 H H H Me 2 —CO—(CH2)4—O-cHx H H
1-1252 H H H Me 2 —CO—(CH2)4—O—Ph H H
1-1253 H H H Me 2 —CO—(CH2)5—O-cHx H H
1-1254 H H H Me 2 —CO—(CH2)5—O—Ph H H
1-1255 H H H Me 2 —CO—(CH2)2—OCH2-cHx H H
1-1256 H H H Me 2 —CO—(CH2)2—OCH2-(4-F-cHx) H H
1-1257 H H H Me 2 —CO—(CH2)2—OCH2-(4-Me-cHx) H H
1-1258 H H H Me 2 —CO—(CH2)2—OCH2-(4-Et-cHx) H H
1-1259 H H H Me 2 —CO—(CH2)2—OCH2-(4-CF3-cHx) H H
1-1260 H H H Me 2 —CO—(CH2)2—OCH2-(4-MeO-cHx) H H
1-1261 H H H Me 2 —CO—(CH2)2—OCH2-(4-EtO-cHx) H H
1-1262 H H H Me 2 —CO—(CH2)2—OCH2-(4-MeS-cHx) H H
1-1263 H H H Me 2 —CO—(CH2)2—OCH2-(4-cHx-cHx) H H
1-1264 H H H Me 2 —CO—(CH2)2—OCH2-(4-Ph-cHx) H H
1-1265 H H H Me 2 —CO—(CH2)2—OCH2—Ph H H
1-1266 H H H Me 2 —CO—(CH2)2—OCH2-(4-F—Ph) H H
1-1267 H H H Me 2 —CO—(CH2)2—OCH2-(4-Me—Ph) H H
1-1268 H H H Me 2 —CO—(CH2)2—OCH2-(4-Et—Ph) H H
1-1269 H H H Me 2 —CO—(CH2)2—OCH2-(4-CF3—Ph) H H
1-1270 H H H Me 2 —CO—(CH2)2—OCH2-(4-MeO—Ph) H H
1-1271 H H H Me 2 —CO—(CH2)2—OCH2-(4-EtO—Ph) H H
1-1272 H H H Me 2 —CO—(CH2)2—OCH2-(4-MeS—Ph) H H
1-1273 H H H Me 2 —CO—(CH2)2—OCH2-(4-cHx-Ph) H H
1-1274 H H H Me 2 —CO—(CH2)2—OCH2-(4-Ph—Ph) H H
1-1275 H H H Me 2 —CO—(CH2)3—OCH2-CH2-cPn H H
1-1276 H H H Me 2 —CO—(CH2)3—OCH2-cHx H H
1-1277 H H H Me 2 —CO—(CH2)3—OCH2-cHx Me H
1-1278 H H H Me 2 —CO—(CH2)3—OCH2-cHx H Me
1-1279 H H H Me 2 —CO—(CH2)3—OCH2-cHx F H
1-1280 H H H Me 2 —CO—(CH2)3—OCH2-cHx H F
1-1281 H H H Me 2 —CO—(CH2)3—OCH2-(3-F-cHx) H H
1-1282 H H H Me 2 —CO—(CH2)3—OCH2-(4-F-cHx) H H
1-1283 H H H Me 2 —CO—(CH2)3—OCH2-(4-Cl-cHx) H H
1-1284 H H H Me 2 —CO—(CH2)3—OCH2-(4-Br-cHx) H H
1-1285 H H H Me 2 —CO—(CH2)3—OCH2-(3-Me-cHx) H H
1-1286 H H H Me 2 —CO—(CH2)3—OCH2-(4-Me-cHx) H H
1-1287 H H H Me 2 —CO—(CH2)3—OCH2-(3-Et-cHx) H H
1-1288 H H H Me 2 —CO—(CH2)3—OCH2-(4-Et-cHx) H H
1-1289 H H H Me 2 —CO—(CH2)3—OCH2-(3-Pr-cHx) H H
1-1290 H H H Me 2 —CO—(CH2)3—OCH2-(4-Pr-cHx) H H
1-1291 H H H Me 2 —CO—(CH2)3—OCH2-(4-iPr-cHx) H H
1-1292 H H H Me 2 —CO—(CH2)3—OCH2-(3-Bu-cHx) H H
1-1293 H H H Me 2 —CO—(CH2)3—OCH2-(4-Bu-cHx) H H
1-1294 H H H Me 2 —CO—(CH2)3—OCH2-(3-CF3-cHx) H H
1-1295 H H H Me 2 —CO—(CH2)3—OCH2-(4-CF3-cHx) H H
1-1296 H H H Me 2 —CO—(CH2)3—OCH2-(3-MeO-cHx) H H
1-1297 H H H Me 2 —CO—(CH2)3—OCH2-(4-MeO-cHx) H H
1-1298 H H H Me 2 —CO—(CH2)3—OCH2-(3-EtO-cHx) H H
1-1299 H H H Me 2 —CO—(CH2)3—OCH2-(4-EtO-cHx) H H
1-1300 H H H Me 2 —CO—(CH2)3—OCH2-(3-PrO-cHx) H H
1-1301 H H H Me 2 —CO—(CH2)3—OCH2-(4-PrO-cHx) H H
1-1302 H H H Me 2 —CO—(CH2)3—OCH2-(3-iPrO-cHx) H H
1-1303 H H H Me 2 —CO—(CH2)3—OCH2-(4-iPrO-cHx) H H
1-1304 H H H Me 2 —CO—(CH2)3—OCH2-[3-(2-Et—PrO)cHx] H H
1-1305 H H H Me 2 —CO—(CH2)3—OCH2-[4-(2-Et—PrO)cHx] H H
1-1306 H H H Me 2 —CO—(CH2)3—OCH2-(3-iBuO-cHx) H H
1-1307 H H H Me 2 —CO—(CH2)3—OCH2-(4-iBuO-cHx) H H
1-1308 H H H Me 2 —CO—(CH2)3—OCH2-(3-MeS-cHx) H H
1-1309 H H H Me 2 —CO—(CH2)3—OCH2-(4-MeS-cHx) H H
1-1310 H H H Me 2 —CO—(CH2)3—OCH2-(3-EtS-cHx) H H
1-1311 H H H Me 2 —CO—(CH2)3—OCH2-(4-EtS-cHx) H H
1-1312 H H H Me 2 —CO—(CH2)3—OCH2-(3-PrS-cHx) H H
1-1313 H H H Me 2 —CO—(CH2)3—OCH2-(4-PrS-cHx) H H
1-1314 H H H Me 2 —CO—(CH2)3—OCH2-(3-iPrS-cHx) H H
1-1315 H H H Me 2 —CO—(CH2)3—OCH2-(4-iPrS-cHx) H H
1-1316 H H H Me 2 —CO—(CH2)3—OCH2-[3-(2-Et—PrS)cHx] H H
1-1317 H H H Me 2 —CO—(CH2)3—OCH2-[4-(2-Et—PrS)cHx] H H
1-1318 H H H Me 2 —CO—(CH2)3—OCH2-(3-iBuS-cHx) H H
1-1319 H H H Me 2 —CO—(CH2)3—OCH2-(4-iBuS-cHx) H H
1-1320 H H H Me 2 —CO—(CH2)3—OCH2-(3-cHx-cHx) H H
1-1321 H H H Me 2 —CO—(CH2)3—OCH2-(4-cHx-cHx) H H
1-1322 H H H Me 2 —CO—(CH2)3—OCH2-(3-Ph-cHx) H H
1-1323 H H H Me 2 —CO—(CH2)3—OCH2-(4-Ph-cHx) H H
1-1324 H H H Me 2 —CO—(CH2)3—OCH2-(2,4-diMe-cHx) H H
1-1325 H H H Me 2 —CO—(CH2)3—OCH2-(3,4-diMe-cHx) H H
1-1326 H H H Me 2 —CO—(CH2)3—OCH2-(3,5-diMe-cHx) H H
1-1327 H H H Me 2 —CO—(CH2)3—OCH2—Ph H H
1-1328 H H H Me 2 —CO—(CH2)3—OCH2—Ph Me H
1-1329 H H H Me 2 —CO—(CH2)3—OCH2—Ph H Me
1-1330 H H H Me 2 —CO—(CH2)3—OCH2—Ph F H
1-1331 H H H Me 2 —CO—(CH2)3—OCH2—Ph H F
1-1332 H H H Me 2 —CO—(CH2)3—OCH2—(3-F—Ph) H H
1-1333 H H H Me 2 —CO—(CH2)3—OCH2-(4-F—Ph) H H
1-1334 H H H Me 2 —CO—(CH2)3—OCH2-(4-Cl—Ph) H H
1-1335 H H H Me 2 —CO—(CH2)3—OCH2-(4-Br—Ph) H H
1-1336 H H H Me 2 —CO—(CH2)3—OCH2-(3-Me—Ph) H H
1-1337 H H H Me 2 —CO—(CH2)3—OCH2-(4-Me—Ph) H H
1-1338 H H H Me 2 —CO—(CH2)3—OCH2-(3-Et—Ph) H H
1-1339 H H H Me 2 —CO—(CH2)3—OCH2-(4-Et—Ph) H H
1-1340 H H H Me 2 —CO—(CH2)3—OCH2-(3-Pr—Ph) H H
1-1341 H H H Me 2 —CO—(CH2)3—OCH2-(4-Pr—Ph) H H
1-1342 H H H Me 2 —CO—(CH2)3—OCH2-(3-iPr—Ph) H H
1-1343 H H H Me 2 —CO—(CH2)3—OCH2-(4-iPr—Ph) H H
1-1344 H H H Me 2 —CO—(CH2)3—OCH2-(3-Bu—Ph) H H
1-1345 H H H Me 2 —CO—(CH2)3—OCH2-(4-Bu—Ph) H H
1-1346 H H H Me 2 —CO—(CH2)3—OCH2-(3-CF3—Ph) H H
1-1347 H H H Me 2 —CO—(CH2)3—OCH2-(4-CF3—Ph) H H
1-1348 H H H Me 2 —CO—(CH2)3—OCH2-(3-MeO—Ph) H H
1-1349 H H H Me 2 —CO—(CH2)3—OCH2-(4-MeO—Ph) H H
1-1350 H H H Me 2 —CO—(CH2)3—OCH2-(3-EtO—Ph) H H
1-1351 H H H Me 2 —CO—(CH2)3—OCH2-(4-EtO—Ph) H H
1-1352 H H H Me 2 —CO—(CH2)3—OCH2-(3-PrO—Ph) H H
1-1353 H H H Me 2 —CO—(CH2)3—OCH2-(4-PrO—Ph) H H
1-1354 H H H Me 2 —CO—(CH2)3—OCH2-(3-iPrO—Ph) H H
1-1355 H H H Me 2 —CO—(CH2)3-OCH2-(4-iPrO—Ph) H H
1-1356 H H H Me 2 —CO—(CH2)3—OCH2-[3-(2-Et—PrO)Ph] H H
1-1357 H H H Me 2 —CO—(CH2)3—OCH2-[4-(2-Et—PrO)Ph] H H
1-1358 H H H Me 2 —CO—(CH2)3—OCH2-(3-iBuO—Ph) H H
1-1359 H H H Me 2 —CO—(CH2)3—OCH2-(4-iBuO—Ph) H H
1-1360 H H H Me 2 —CO—(CH2)3—OCH2-(3-MeS—Ph) H H
1-1361 H H H Me 2 —CO—(CH2)3—OCH2-(4-MeS—Ph) H H
1-1362 H H H Me 2 —CO—(CH2)3—OCH2-(3-EtS—Ph) H H
1-1363 H H H Me 2 —CO—(CH2)3—OCH2-(4-EtS—Ph) H H
1-1364 H H H Me 2 —CO—(CH2)3—OCH2-(3-PrS—Ph) H H
1-1365 H H H Me 2 —CO—(CH2)3—OCH2-(4-PrS—Ph) H H
1-1366 H H H Me 2 —CO—(CH2)3—OCH2-(3-iPrS—Ph) H H
1-1367 H H H Me 2 —CO—(CH2)3—OCH2-(4-iPrS—Ph) H H
1-1368 H H H Me 2 —CO—(CH2)3—OCH2-[3-(2-Et—PrS)Ph] H H
1-1369 H H H Me 2 —CO—(CH2)3—OCH2-[4-(2-Et—PrS)Ph] H H
1-1370 H H H Me 2 —CO—(CH2)3—OCH2-(3-iBuS—Ph) H H
1-1371 H H H Me 2 —CO—(CH2)3—OCH2-(4-iBuS—Ph) H H
1-1372 H H H Me 2 —CO—(CH2)3—OCH2-(3-cHx-Ph) H H
1-1373 H H H Me 2 —CO—(CH2)3—OCH2-(4-cHx-Ph) H H
1-1374 H H H Me 2 —CO—(CH2)3—OCH2-(3-Ph—Ph) H H
1-1375 H H H Me 2 —CO—(CH2)3—OCH2-(4-Ph—Ph) H H
1-1376 H H H Me 2 —CO—(CH2)3—OCH2-(2,4-diMe—Ph) H H
1-1377 H H H Me 2 —CO—(CH2)3—OCH2-(3,4-diMe—Ph) H H
1-1378 H H H Me 2 —CO—(CH2)3—OCH2-(3,5-diMe—Ph) H H
1-1379 H H H Me 2 —CO—(CH2)4—OCH2-cHx H H
1-1380 H H H Me 2 —CO—(CH2)4—OCH2—Ph H H
1-1381 H H H Me 2 —CO—(CH2)5—OCH2-cHx H H
1-1382 H H H Me 2 —CO—(CH2)5—OCH2—Ph H H
1-1383 H H H Me 2 —CH(OH)—CH2-cHx H H
1-1384 H H H Me 2 —CH(OH)—CH2—Ph H H
1-1385 H H H Me 2 —CH(OH)—(CH2)2-cHx H H
1-1386 H H H Me 2 —CH(OH)—(CH2)2—Ph H H
1-1387 H H H Me 2 —CH(OH)—(CH2)3-cHx H H
1-1388 H H H Me 2 —CH(OH)—(CH2)3—Ph H H
1-1389 H H H Me 2 —CH(OH)—(CH2)4-cHx H H
1-1390 H H H Me 2 —CH(OH)—(CH2)4-(4-F-cHx) H H
1-1391 H H H Me 2 —CH(OH)—(CH2)4-(4-Me-cHx) H H
1-1392 H H H Me 2 —CH(OH)—(CH2)4-(4-Et-cHx) H H
1-1393 H H H Me 2 —CH(OH)—(CH2)4-(4-CF3-cHx) H H
1-1394 H H H Me 2 —CH(OH)—(CH2)4-(4-MeO-cHx) H H
1-1395 H H H Me 2 —CH(OH)—(CH2)4-(4-EtO-cHx) H H
1-1396 H H H Me 2 —CH(OH)—(CH2)4-(4-MeS-cHx) H H
1-1397 H H H Me 2 —CH(OH)—(CH2)4-(4-cHx-cHx) H H
1-1398 H H H Me 2 —CH(OH)—(CH2)4-(4-Ph-cHx) H H
1-1399 H H H Me 2 —CH(OH)—(CH2)4—Ph H H
1-1400 H H H Me 2 —CH(OH)—(CH2)4-(4-F—Ph) H H
1-1401 H H H Me 2 —CH(OH)—(CH2)4-(4-Me—Ph) H H
1-1402 H H H Me 2 —CH(OH)—(CH2)4-(4-Et—Ph) H H
1-1403 H H H Me 2 —CH(OH)—(CH2)4-(4-CF3—Ph) H H
1-1404 H H H Me 2 —CH(OH)—(CH2)4-(4-MeO—Ph) H H
1-1405 H H H Me 2 —CH(OH)—(CH2)4-(4-EtO—Ph) H H
1-1406 H H H Me 2 —CH(OH)—(CH2)4-(4-MeS—Ph) H H
1-1407 H H H Me 2 —CH(OH)—(CH2)4-(4-cHx-Ph) H H
1-1408 H H H Me 2 —CH(OH)—(CH2)4-(4-Ph—Ph) H H
1-1409 H H H Me 2 —CH(OH)—(CH2)5-cHx H H
1-1410 H H H Me 2 —CH(OH)—(CH2)5-(4-F-cHx) H H
1-1411 H H H Me 2 —CH(OH)—(CH2)5-(4-Me-cHx) H H
1-1412 H H H Me 2 —CH(OH)—(CH2)5-(4-Et-cHx) H H
1-1413 H H H Me 2 —CH(OH)—(CH2)5-(4-CF3-cHx) H H
1-1414 H H H Me 2 —CH(OH)—(CH2)5-(4-MeO-cHx) H H
1-1415 H H H Me 2 —CH(OH)—(CH2)5-(4-EtO-cHx) H H
1-1416 H H H Me 2 —CH(OH)—(CH2)5-(4-MeS-cHx) H H
1-1417 H H H Me 2 —CH(OH)—(CH2)5-(4-cHx-cHx) H H
1-1418 H H H Me 2 —CH(OH)—(CH2)5-(4-Ph-cHx) H H
1-1419 H H H Me 2 —CH(OH)—(CH2)5—Ph H H
1-1420 H H H Me 2 —CH(OH)—(CH2)5—(4-F—Ph) H H
1-1421 H H H Me 2 —CH(OH)—(CH2)5-(4-Me—Ph) H H
1-1422 H H H Me 2 —CH(OH)—(CH2)5-(4-Et—Ph) H H
1-1423 H H H Me 2 —CH(OH)—(CH2)5-(4-CF3—Ph) H H
1-1424 H H H Me 2 —CH(OH)—(CH2)5-(4-MeO—Ph) H H
1-1425 H H H Me 2 —CH(OH)—(CH2)5-(4-EtO—Ph) H H
1-1426 H H H Me 2 —CH(OH)—(CH2)5-(4-MeS—Ph) H H
1-1427 H H H Me 2 —CH(OH)—(CH2)5-(4-cHx-Ph) H H
1-1428 H H H Me 2 —CH(OH)—(CH2)5-(4-Ph—Ph) H H
1-1429 H H H Me 2 —CH(OH)—(CH2)6-cHx H H
1-1430 H H H Me 2 —CH(OH)—(CH2)6—Ph H H
1-1431 H H H Me 2 —CH(OH)—(CH2)7-cHx H H
1-1432 H H H Me 2 —CH(OH)—(CH2)7—Ph H H
1-1433 H H H Me 2 -4-(cHx-CH2O)Ph H H
1-1434 H H H Me 2 -4-(cHx-CH2O)-2-F—Ph H H
1-1435 H H H Me 2 -4-(cHx-CH2O)-3-F—Ph H H
1-1436 H H H Me 2 -4-(cHx-CH2O)-2,3-diF—Ph H H
1-1437 H H H Me 2 -4-(cHx-CH2O)-2-Cl—Ph H H
1-1438 H H H Me 2 -4-(cHx-CH2O)-3-Cl—Ph H H
1-1439 H H H Me 2 -4-(cHx-CH2O)-2,3-diCl—Ph H H
1-1440 H H H Me 2 -4-(cHx-CH2O)-2-Me—Ph H H
1-1441 H H H Me 2 -4-(cHx-CH2O) -3-Me—Ph H H
1-1442 H H H Me 2 -4-(cHx-CH2O)-2,3-diMe—Ph H H
1-1443 H H H Me 2 -4-[cHx-(CH2)2O]Ph H H
1-1444 H H H Me 2 -3-[cHx-(CH2)2O]Ph H H
1-1445 H H H Me 2 -(4-BzO—Ph) H H
1-1446 H H H Me 2 -(4-BzO-2-F—Ph) H H
1-1447 H H H Me 2 -(4-BzO-3-F—Ph) H H
1-1448 H H H Me 2 -(4-BzO-2,3-diF—Ph) H H
1-1449 H H H Me 2 -(4-BzO-2-Cl—Ph) H H
1-1450 H H H Me 2 -(4-BzO-3-Cl—Ph) H H
1-1451 H H H Me 2 -(4-BzO-2,3-diCl—Ph) H H
1-1452 H H H Me 2 -(4-BzO-2-Me—Ph) H H
1-1453 H H H Me 2 -(4-BzO-3-Me—Ph) H H
1-1454 H H H Me 2 -(4-BzO-2,3-diMe—Ph) H H
1-1455 H H H Me 2 -4-[Ph-(CH2)2O]—Ph H H
1-1456 H H H Me 2 -4-[Ph-(CH2)3O]—Ph H H
1-1457 H H H Et 2 —(CH2)3-cHx H H
1-1458 H H H Et 2 —(CH2)3—Ph H H
1-1459 H H H Et 2 —(CH2)4-cHx H H
1-1460 H H H Et 2 —(CH2)4—Ph H H
1-1461 H H H Et 2 —(CH2)5-cPn H H
1-1462 H H H Et 2 —(CH2)5-cHx H H
1-1463 H H H Et 2 —(CH2)5-cHx Me H
1-1464 H H H Et 2 —(CH2)5-cHx H Me
1-1465 H H H Et 2 —(CH2)5-cHx F H
1-1466 H H H Et 2 —(CH2)5-cHx H F
1-1467 H H H Et 2 —(CH2)5-(4-F-cHx) H H
1-1468 H H H Et 2 —(CH2)5-(4-Cl-cHx) H H
1-1469 H H H Et 2 —(CH2)5-(4-Br-cHx) H H
1-1470 H H H Et 2 —(CH2)5-(4-Me-cHx) H H
1-1471 H H H Et 2 —(CH2)5-(4-Et-cHx) H H
1-1472 H H H Et 2 —(CH2)5-(4-Pr-cHx) H H
1-1473 H H H Et 2 —(CH2)5-(4-iPr-cHx) H H
1-1474 H H H Et 2 —(CH2)5-(4-CF3-cHx) H H
1-1475 H H H Et 2 —(CH2)5-(4-MeO-cHx) H H
1-1476 H H H Et 2 —(CH2)5-(4-EtO-cHx) H H
1-1477 H H H Et 2 —(CH2)5-(4-PrO-cHx) H H
1-1478 H H H Et 2 —(CH2)5-(4-iPrO-cHx) H H
1-1479 H H H Et 2 —(CH2)5-(3-MeS-cHx) H H
1-1480 H H H Et 2 —(CH2)5-(4-MeS-cHx) H H
1-1481 H H H Et 2 —(CH2)5-(2,4-diMe-cHx) H H
1-1482 H H H Et 2 —(CH2)5-(3,4-diMe-cHx) H H
1-1483 H H H Et 2 —(CH2)5-(3,5-diMe-cHx) H H
1-1484 H H H Et 2 —(CH2)5—Ph H H
1-1485 H H H Et 2 —(CH2)5—Ph Me H
1-1486 H H H Et 2 —(CH2)5—Ph H Me
1-1487 H H H Et 2 —(CH2)5—Ph F H
1-1488 H H H Et 2 —(CH2)5—Ph H F
1-1489 H H H Et 2 —(CH2)5-(4-F—Ph) H H
1-1490 H H H Et 2 —(CH2)5-(4-Cl—Ph) H H
1-1491 H H H Et 2 —(CH2)5-(4-Br—Ph) H H
1-1492 H H H Et 2 —(CH2)5-(4-Me—Ph) H H
1-1493 H H H Et 2 —(CH2)5-(4-Et—Ph) H H
1-1494 H H H Et 2 —(CH2)5-(4-Pr—Ph) H H
1-1495 H H H Et 2 —(CH2)5-(4-iPr—Ph) H H
1-1496 H H H Et 2 —(CH2)5-(4-Bu—Ph) H H
1-1497 H H H Et 2 —(CH2)5-(4-CF3—Ph) H H
1-1498 H H H Et 2 —(CH2)5-(4-MeO—Ph) H H
1-1499 H H H Et 2 —(CH2)5-(4-EtO—Ph) H H
1-1500 H H H Et 2 —(CH2)5-(4-PrO—Ph) H H
1-1501 H H H Et 2 —(CH2)5-(4-iPrO—Ph) H H
1-1502 H H H Et 2 —(CH2)5-(3-MeS—Ph) H H
1-1503 H H H Et 2 —(CH2)5-(4-MeS—Ph) H H
1-1504 H H H Et 2 —(CH2)5-(2,4-diMe—Ph) H H
1-1505 H H H Et 2 —(CH2)5-(3,4-diMe—Ph) H H
1-1506 H H H Et 2 —(CH2)5-(3,5-diMe-Ph) H H
1-1507 H H H Et 2 —(CH2)6-cPn H H
1-1508 H H H Et 2 —(CH2)6-cHx H H
1-1509 H H H Et 2 —(CH2)6-cHx Me H
1-1510 H H H Et 2 —(CH2)6-cHx H Me
1-1511 H H H Et 2 —(CH2)6-cHx F H
1-1512 H H H Et 2 —(CH2)6-cHx H F
1-1513 H H H Et 2 —(CH2)6-(4-F-cHx) H H
1-1514 H H H Et 2 —(CH2)6-(4-Cl-cHx) H H
1-1515 H H H Et 2 —(CH2)6-(4-Br-cHx) H H
1-1516 H H H Et 2 —(CH2)6-(4-Me-cHx) H H
1-1517 H H H Et 2 —(CH2)6-(4-Et-cHx) H H
1-1518 H H H Et 2 —(CH2)6-(4-Pr-cHx) H H
1-1519 H H H Et 2 —(CH2)6-(4-iPr-cHx) H H
1-1520 H H H Et 2 —(CH2)6-(4-Bu-cHx) H H
1-1521 H H H Et 2 —(CH2)6-(4-CF3-cHx) H H
1-1522 H H H Et 2 —(CH2)6-(4-MeO-cHx) H H
1-1523 H H H Et 2 —(CH2)6-(4-EtO-cHx) H H
1-1524 H H H Et 2 —(CH2)6-(4-PrO-cHx) H H
1-1525 H H H Et 2 —(CH2)6-(4-iPrO-cHx) H H
1-1526 H H H Et 2 —(CH2)6-(3-MeS-cHx) H H
1-1527 H H H Et 2 —(CH2)6-(4-MeS-cHx) H H
1-1528 H H H Et 2 —(CH2)6-(2,4-diMe-cHx) H H
1-1529 H H H Et 2 —(CH2)6-(3,4-diMe-cHx) H H
1-1530 H H H Et 2 —(CH2)6-(3,5-diMe-cHx) H H
1-1531 H H H Et 2 —(CH2)6—Ph H H
1-1532 H H H Et 2 —(CH2)6—Ph Me H
1-1533 H H H Et 2 —(CH2)6—Ph H Me
1-1534 H H H Et 2 —(CH2)6—Ph F H
1-1535 H H H Et 2 —(CH2)6—Ph H F
1-1536 H H H Et 2 —(CH2)6-(4-F—Ph) H H
1-1537 H H H Et 2 —(CH2)6-(4-Cl—Ph) H H
1-1538 H H H Et 2 —(CH2)6-(4-Br—Ph) H H
1-1539 H H H Et 2 —(CH2)6-(4-Me—Ph) H H
1-1540 H H H Et 2 —(CH2)6-(4-Et—Ph) H H
1-1541 H H H Et 2 —(CH2)6-(4-Pr—Ph) H H
1-1542 H H H Et 2 —(CH2)6-(4-iPr—Ph) H H
1-1543 H H H Et 2 —(CH2)6-(4-Bu—Ph) H H
1-1544 H H H Et 2 —(CH2)6-(4-CF3—Ph) H H
1-1545 H H H Et 2 —(CH2)6-(4-MeO—Ph) H H
1-1546 H H H Et 2 —(CH2)6-(4-EtO—Ph) H H
1-1547 H H H Et 2 —(CH2)6-(4-PrO—Ph) H H
1-1548 H H H Et 2 —(CH2)6-(4-iPrO—Ph) H H
1-1549 H H H Et 2 —(CH2)6-(3-MeS—Ph) H H
1-1550 H H H Et 2 —(CH2)6-(4-MeS—Ph) H H
1-1551 H H H Et 2 —(CH2)6-(2,4-diMe—Ph) H H
1-1552 H H H Et 2 —(CH2)6-(3,4-diMe—Ph) H H
1-1553 H H H Et 2 —(CH2)6-(3,5-diMe—Ph) H H
1-1554 H H H Et 2 —(CH2)7-cHx H H
1-1555 H H H Et 2 —(CH2)7—Ph H H
1-1556 H H H Et 2 —C≡C—CH2-cHx H H
1-1557 H H H Et 2 —C≡C—CH2—Ph H H
1-1558 H H H Et 2 —C≡C—(CH2)2-cHx H H
1-1559 H H H Et 2 —C≡C—(CH2)2-Ph H H
1-1560 H H H Et 2 —C≡C—(CH2)3-cPn H H
1-1561 H H H Et 2 —C≡C—(CH2)3-cHx H H
1-1562 H H H Et 2 —C≡C—(CH2)3-cHx Me H
1-1563 H H H Et 2 —C≡C—(CH2)3-cHx H Me
1-1564 H H H Et 2 —C≡C—(CH2)3-cHx F H
1-1565 H H H Et 2 —C≡C—(CH2)3-cHx H F
1-1566 H H H Et 2 —C≡C—(CH2)3-(4-F-cHx) H H
1-1567 H H H Et 2 —C≡C—(CH2)3-(4-Cl-cHx) H H
1-1568 H H H Et 2 —C≡C—(CH2)3-(4-Br-cHx) H H
1-1569 H H H Et 2 —C≡C—(CH2)3-(4-Me-cHx) H H
1-1570 H H H Et 2 —C≡C—(CH2)3-(4-Et-cHx) H H
1-1571 H H H Et 2 —C≡C—(CH2)3-(4-Pr-cHx) H H
1-1572 H H H Et 2 —C≡C—(CH2)3-(4-iPr-cHx) H H
1-1573 H H H Et 2 —C≡C—(CH2)3-(4-Bu-cHx) H H
1-1574 H H H Et 2 —C≡C—(CH2)3-(4-CF3-cHx) H H
1-1575 H H H Et 2 —C≡C—(CH2)3-(4-MeO-cHx) H H
1-1576 H H H Et 2 —C≡C—(CH2)3-(4-EtO-cHx) H H
1-1577 H H H Et 2 —C≡C—(CH2)3-(4-PrO-cHx) H H
1-1578 H H H Et 2 —C≡C—(CH2)3-(4-iPrO-cHx) H H
1-1579 H H H Et 2 —C≡C—(CH2)3-(3-MeS-cHx) H H
1-1580 H H H Et 2 —C≡C—(CH2)3-(4-MeS-cHx) H H
1-1581 H H H Et 2 —C≡C—(CH2)3-(2,4-diMe-cHx) H H
1-1582 H H H Et 2 —C≡C—(CH2)3-(3,4-diMe-cHx) H H
1-1583 H H H Et 2 —C≡C—(CH2)3-(3,5-diMe-cHx) H H
1-1584 H H H Et 2 —C≡C—(CH2)3—Ph H H
1-1585 H H H Et 2 —C≡C—(CH2)3—Ph Me H
1-1586 H H H Et 2 —C≡C—(CH2)3—Ph H Me
1-1587 H H H Et 2 —C≡C—(CH2)3—Ph F H
1-1588 H H H Et 2 —C≡C—(CH2)3—Ph H F
1-1589 H H H Et 2 —C≡C—(CH2)3-(4-F—Ph) H H
1-1590 H H H Et 2 —C≡C—(CH2)3-(4-Cl—Ph) H H
1-1591 H H H Et 2 —C≡C—(CH2)3-(4-Br—Ph) H H
1-1592 H H H Et 2 —C≡C—(CH2)3-(4-Me—Ph) H H
1-1593 H H H Et 2 —C≡C—(CH2)3-(4-Et—Ph) H H
1-1594 H H H Et 2 —C≡C—(CH2)3-(4-Pr—Ph) H H
1-1595 H H H Et 2 —C≡C—(CH2)3-(4-iPr—Ph) H H
1-1596 H H H Et 2 —C≡C—(CH2)3-(4-Bu—Ph) H H
1-1597 H H H Et 2 —C≡C—(CH2)3-(4-CF3—Ph) H H
1-1598 H H H Et 2 —C≡C—(CH2)3-(4-MeO—Ph) H H
1-1599 H H H Et 2 —C≡C—(CH2)3-(4-EtO—Ph) H H
1-1600 H H H Et 2 —C≡C—(CH2)3-(4-PrO—Ph) H H
1-1601 H H H Et 2 —C≡C—(CH2)3-(4-iPrO—Ph) H H
1-1602 H H H Et 2 —C≡C—(CH2)3-(3-MeS—Ph) H H
1-1603 H H H Et 2 —C≡C—(CH2)3-(4-MeS—Ph) H H
1-1604 H H H Et 2 —C≡C—(CH2)3-(2,4-diMe—Ph) H H
1-1605 H H H Et 2 —C≡C—(CH2)3-(3,4-diMe—Ph) H H
1-1606 H H H Et 2 —C≡C—(CH2)3-(3,5-diMe—Ph) H H
1-1607 H H H Et 2 —C≡C—(CH2)4-cPn H H
1-1608 H H H Et 2 —C≡C—(CH2)4-cHx H H
1-1609 H H H Et 2 —C≡C—(CH2)4-cHx Me H
1-1610 H H H Et 2 —C≡C—(CH2)4-cHx H Me
1-1611 H H H Et 2 —C≡C—(CH2)4-cHx F H
1-1612 H H H Et 2 —C≡C—(CH2)4-cHx H F
1-1613 H H H Et 2 —C≡C—(CH2)4-(4-F-cHx) H H
1-1614 H H H Et 2 —C≡C—(CH2)4-(4-Cl-cHx) H H
1-1615 H H H Et 2 —C≡C—(CH2)4-(4-Br-cHx) H H
1-1616 H H H Et 2 —C≡C—(CH2)4-(4-Me-cHx) H H
1-1617 H H H Et 2 —C≡C—(CH2)4-(4-Et-cHx) H H
1-1618 H H H Et 2 —C≡C—(CH2)4-(4-Pr-cHx) H H
1-1619 H H H Et 2 —C≡C—(CH2)4-(4-ipr-cHx) H H
1-1620 H H H Et 2 —C≡C—(CH2)4-(4-Bu-cHx) H H
1-1621 H H H Et 2 —C≡C—(CH2)4-(4-CF3-cHx) H H
1-1622 H H H Et 2 —C≡C—(CH2)4-(4-MeO-cHx) H H
1-1623 H H H Et 2 —C≡C—(CH2)4-(4-EtO-cHx) H H
1-1624 H H H Et 2 —C≡C—(CH2)4-(4-PrO-cHx) H H
1-1625 H H H Et 2 —C≡C—(CH2)4-(4-iPrO-cHx) H H
1-1626 H H H Et 2 —C≡C—(CH2)4-(4-MeS-cHx) H H
1-1627 H H H Et 2 —C≡C—(CH2)4-(2,4-diMe-cHx) H H
1-1628 H H H Et 2 —C≡C—(CH2)4-(3,4-diMe-cHx) H H
1-1629 H H H Et 2 —C≡C—(CH2)4-(3,5-diMe-cHx) H H
1-1630 H H H Et 2 —C≡C—(CH2)4—Ph H H
1-1631 H H H Et 2 —C≡C—(CH2)4—Ph Me H
1-1632 H H H Et 2 —C≡C—(CH2)4—Ph H Me
1-1633 H H H Et 2 —C≡C—(CH2)4—Ph F H
1-1634 H H H Et 2 —C≡C—(CH2)4—Ph H F
1-1635 H H H Et 2 —C≡C—(CH2)4-(4-F—Ph) H H
1-1636 H H H Et 2 —C≡C—(CH2)4-(4-Cl—Ph) H H
1-1637 H H H Et 2 —C≡C—(CH2)4-(4-Br—Ph) H H
1-1638 H H H Et 2 —C≡C—(CH2)4-(4-Me—Ph) H H
1-1639 H H H Et 2 —C≡C—(CH2)4-(4-Et—Ph) H H
1-1640 H H H Et 2 —C≡C—(CH2)4-(4-Pr—Ph) H H
1-1641 H H H Et 2 —C≡C—(CH2)4-(4-iPr—Ph) H H
1-1642 H H H Et 2 —C≡C—(CH2)4-(4—Bu—Ph) H H
1-1643 H H H Et 2 —C≡C—(CH2)4-(4-CF3—Ph) H H
1-1644 H H H Et 2 —C≡C—(CH2)4-(4-MeO—Ph) H H
1-1645 H H H Et 2 —C≡C—(CH2)4-(4-EtO—Ph) H H
1-1646 H H H Et 2 —C≡C—(CH2)4-(4-PrO—Ph) H H
1-1647 H H H Et 2 —C≡C—(CH2)4-(4-iPrO—Ph) H H
1-1648 H H H Et 2 —C≡C—(CH2)4-(3—MeS—Ph) H H
1-1649 H H H Et 2 —C≡C—(CH2)4-(4-MeS—Ph) H H
1-1650 H H H Et 2 —C≡C—(CH2)4-(2,4-diMe—Ph) H H
1-1651 H H H Et 2 —C≡C—(CH2)4-(3,4-diMe—Ph) H H
1-1652 H H H Et 2 —C≡C—(CH2)4-(3,5-diMe—Ph) H H
1-1653 H H H Et 2 —C≡C—(CH2)5-cHx H H
1-1654 H H H Et 2 —C≡C—(CH2)5—Ph H H
1-1655 H H H Et 2 —C≡C—(CH2)6-cHx H H
1-1656 H H H Et 2 —C≡C—(CH2)6—Ph H H
1-1657 H H H Et 2 —C≡C—CH2O-cHx H H
1-1658 H H H Et 2 —C≡C—CH2O—Ph H H
1-1659 H H H Et 2 —C≡C—(CH2)2O-cPn H H
1-1660 H H H Et 2 —C≡C—(CH2)2O-cHx H H
1-1661 H H H Et 2 —C≡C—(CH2)2O-cHx Me H
1-1662 H H H Et 2 —C≡C—(CH2)2O-cHx H Me
1-1663 H H H Et 2 —C≡C—(CH2)2O-cHx F H
1-1664 H H H Et 2 —C≡C—(CH2)2O-cHx H F
1-1665 H H H Et 2 —C≡C—(CH2)2O-(4-F-cHx) H H
1-1666 H H H Et 2 —C≡C—(CH2)2O-4-Cl-cHx) H H
1-1667 H H H Et 2 —C≡C—(CH2)2O-(4-Br-cHx) H H
1-1668 H H H Et 2 —C≡C—(CH2)2O-(4-Me-cHx) H H
1-1669 H H H Et 2 —C≡C—(CH2)2O-(4-Et-cHx) H H
1-1670 H H H Et 2 —C≡C—(CH2)2O-(4-Pr-cHx) H H
1-1671 H H H Et 2 —C≡C—(CH2)2O-(4-iPr-cHx) H H
1-1672 H H H Et 2 —C≡C—(CH2)2O-(4-Bu-cHx) H H
1-1673 H H H Et 2 —C≡C—(CH2)2O-(4-CF3-cHx) H H
1-1674 H H H Et 2 —C≡C—(CH2)2O-(4-MeO-cHx) H H
1-1675 H H H Et 2 —C≡C—(CH2)2O-(4-EtO-cHx) H H
1-1676 H H H Et 2 —C≡C—(CH2)2O-(4-PrO-cHx) H H
1-1677 H H H Et 2 —C≡C—(CH2)2O-(4-iPrO-cHx) H H
1-1678 H H H Et 2 —C≡C—(CH2)2O-(3-MeS-cHx) H H
1-1679 H H H Et 2 —C≡C—(CH2)2O-(4-MeS-cHx) H H
1-1680 H H H Et 2 —C≡C—(CH2)2O-(2,4-diMe-cHx) H H
1-1681 H H H Et 2 —C≡C—(CH2)2O-(3,4-diMe-cHx) H H
1-1682 H H H Et 2 —C≡C—(CH2)2O-(3,5-diMe-cHx) H H
1-1683 H H H Et 2 —C≡C—(CH2)2O—Ph H H
1-1684 H H H Et 2 —C≡C—(CH2)2O—Ph Me H
1-1685 H H H Et 2 —C≡C—(CH2)2O—Ph H Me
1-1686 H H H Et 2 —C≡C—(CH2)2O—Ph F H
1-1687 H H H Et 2 —C≡C—(CH2)2O—Ph H F
1-1688 H H H Et 2 —C≡C—(CH2)2O-(4-F—Ph) H H
1-1689 H H H Et 2 —C≡C—(CH2)2O-(4-Cl—Ph) H H
1-1690 H H H Et 2 —C≡C—(CH2)2O-(4-Br—Ph) H H
1-1691 H H H Et 2 —C≡C—(CH2)2O-(4-Me—Ph) H H
1-1692 H H H Et 2 —C≡C—(CH2)2O-(4-Et—Ph) H H
1-1693 H H H Et 2 —C≡C—(CH2)2O-(4-Pr—Ph) H H
1-1694 H H H Et 2 —C≡C—(CH2)2O-(4-iPr—Ph) H H
1-1695 H H H Et 2 —C≡C—(CH2)2O-(4-Bu—Ph) H H
1-1696 H H H Et 2 —C≡C—(CH2)2O-(4-CF3—Ph) H H
1-1697 H H H Et 2 —C≡C—(CH2)2O-(4-MeO—Ph) H H
1-1698 H H H Et 2 —C≡C—(CH2)2O-(4-EtO—Ph) H H
1-1699 H H H Et 2 —C≡C—(CH2)2O-(4-Pro—Ph) H H
1-1700 H H H Et 2 —C≡C—(CH2)2O-(4-iPrO—Ph) H H
1-1701 H H H Et 2 —C≡C—(CH2)2O-(4-MeS—Ph) H H
1-1702 H H H Et 2 —C≡C—(CH2)2O-(2,4-diMe—Ph) H H
1-1703 H H H Et 2 —C≡C—(CH2)2O-(3,4-diMe—Ph) H H
1-1704 H H H Et 2 —C≡C—(CH2)2O-(3,5-diMe—Ph) H H
1-1705 H H H Et 2 —CO—(CH2)3-cHx H H
1-1706 H H H Et 2 —CO—(CH2)3—Ph H H
1-1707 H H H Et 2 —CO—(CH2)4-cHx H H
1-1708 H H H Et 2 ——CO—(CH2)4—Ph H H
1-1709 H H H Et 2 —CO—(CH2)5-cHx H H
1-1710 H H H Et 2 —CO—(CH2)5—Ph H H
1-1711 H H H Et 2 —CH(OH)—(CH2)4-cHx H H
1-1712 H H H Et 2 —CH(OH)—(CH2)4—Ph H H
1-1713 H H H Et 2 —CH(OH)—(CH2)5-cHx H H
1-1714 H H H Et 2 —CH(OH)—(CH2)5—Ph H H
1-1715 H H H Et 2 -4-(cHx-CH2O)Ph H H
1-1716 H H H Et 2 -4-[cHx-(CH2)2O]Ph H H
1-1717 H H H Et 2 -4-[cHx-(CH2)3O]Ph H H
1-1718 H H H Et 2 -(4-BzO—Ph) H H
1-1719 H H H Et 2 -(4-BzO-2-F—Ph) H H
1-1720 H H H Et 2 -(4-BzO-3-F—Ph) H H
1-1721 H H H Et 2 -(4-BzO-2,3-diF—Ph) H H
1-1722 H H H Et 2 -(4-BzO-2-Cl—Ph) H H
1-1723 H H H Et 2 -(4-BzO-3-Cl—Ph) H H
1-1724 H H H Et 2 -(4-BzO-2,3-diCl—Ph) H H
1-1725 H H H Et 2 -(4-BzO-2-Me—Ph) H H
1-1726 H H H Et 2 -(4-BzO-3-Me—Ph) H H
1-1727 H H H Et 2 -(4-BzO-2,3-diMe—Ph) H H
1-1728 H H H Et 2 -4-[Ph—(CH2)2O]—Ph H H
1-1729 H H H Et 2 -4-[Ph—(CH2)3O]—Ph H H
1-1730 H H H Pr 2 —(CH2)5-cHx H H
1-1731 H H H Pr 2 —(CH2)5—Ph H H
1-1732 H H H Pr 2 —(CH2)6-cHx H H
1-1733 H H H Pr 2 —(CH2)6—Ph H H
1-1734 H H H Pr 2 —C≡C—CH2-cHx H H
1-1735 H H H Pr 2 —C≡C—(CH2)3-cHx H H
1-1736 H H H Pr 2 —C≡C—(CH2)3—Ph H H
1-1737 H H H Pr 2 —C≡C—(CH2)4-cHx H H
1-1738 H H H Pr 2 —C≡C—(CH2)4—Ph H H
1-1739 H H H Pr 2 —C≡C—(CH2)2O—cHx H H
1-1740 H H H Pr 2 —C≡C—(CH2)2O—Ph H H
1-1741 H H H Pr 2 -4-(cHx-CH2O)Ph H H
1-1742 H H H Pr 2 -(4-BzO—Ph) H H
1-1743 H H H Me 2 —(CH2)4-(3-F—Ph) H H
1-1744 H H H Me 2 —(CH2)4-(3,4-diF—Ph) H H
1-1745 H H H Me 2 —(CH2)4-(3,5-diF—Ph) H H
1-1746 H H H Me 2 —(CH2)4-(3-Cl—Ph) H H
1-1747 H H H Me 2 —(CH2)4-(4-Cl—Ph) H H
1-1748 H H H Me 2 —(CH2)4-(3,4-diCl—Ph) H H
1-1749 H H H Me 2 —(CH2)4-(3,5-diCl—Ph) H H
1-1750 H H H Me 2 —(CH2)4-(3-Me—Ph) H H
1-1751 H H H Me 2 —(CH2)4-(3,4-diMe—Ph) H H
1-1752 H H H Me 2 —(CH2)4-(3,5-diMe—Ph) H H
1-1753 H H H Me 2 —(CH2)4-(3-CF3—Ph) H H
1-1754 H H H Me 2 —(CH2)4-(3,4-diCF3—Ph) H H
1-1755 H H H Me 2 —(CH2)4-(3,5-diCF3—Ph) H H
1-1756 H H H Me 2 —(CH2)4-(3-MeO—Ph) H H
1-1757 H H H Me 2 —(CH2)4-(3,4-diMeO—Ph) H H
1-1758 H H H Me 2 —(CH2)4-(3,5-diMeO—Ph) H H
1-1759 H H H Me 2 —(CH2)4-(3,4,5-triMeO—Ph) H H
1-1760 H H H Me 2 —(CH2)4-(3-Ac—Ph) H H
1-1761 H H H Me 2 —(CH2)4-(4-Ac—Ph) H H
1-1762 H H H Me 2 —(CH2)5-(3,4-diF—Ph) H H
1-1763 H H H Me 2 —(CH2)5-(3,5-diF—Ph) H H
1-1764 H H H Me 2 —(CH2)5-(3-Cl—Ph) H H
1-1765 H H H Me 2 —(CH2)5-(3,4-diCl—Ph) H H
1-1766 H H H Me 2 —(CH2)5-(3,5-diCl—Ph) H H
1-1767 H H H Me 2 —(CH2)5-(3,4-diCF3—Ph) H H
1-1768 H H H Me 2 —(CH2)5-(3,5-diCF3—Ph) H H
1-1769 H H H Me 2 —(CH2)5-(3,4-diMeO—Ph) H H
1-1770 H H H Me 2 —(CH2)5-(3,5-diMeO—Ph) H H
1-1771 H H H Me 2 —(CH2)s-(3,4,5-triMeO—Ph) H H
1-1772 H H H Me 2 —(CH2)5-(3-Ac—Ph) H H
1-1773 H H H Me 2 —(CH2)5-(4-Ac—Ph) H H
1-1774 H H H Me 2 —(CH2)3—O-(3-F—Ph) H H
1-1775 H H H Me 2 —(CH2)3—O-(3,4-diF—Ph) H H
1-1776 H H H Me 2 —(CH2)3—O-(3,5-diF—Ph) H H
1-1777 H H H Me 2 —(CH2)3—O-(3-Me—Ph) H H
1-1778 H H H Me 2 —(CH2)3—O-(3,4-diMe—Ph) H H
1-1779 H H H Me 2 —(CH2)3-O-(3,5-diMe—Ph) H H
1-1780 H H H Me 2 —(CH2)3—O-(3-CF3—Ph) H H
1-1781 H H H Me 2 —(CH2)3—O-(3,4-diCF3—Ph) H H
1-1782 H H H Me 2 —(CH2)3—O-(3,5-diCF3—Ph) H H
1-1783 H H H Me 2 —(CH2)3—O-(3-MeO—Ph) H H
1-1784 H H H Me 2 —(CH2)3—O-(3,4-diMeO—Ph) H H
1-1785 H H H Me 2 —(CH2)a-O-(3,5-diMeO—Ph) H H
1-1786 H H H Me 2 —(CH2)3—O-(3,4,5-triMeO—Ph) H H
1-1787 H H H Me 2 —(CH2)3—O-(3-Ac—Ph) H H
1-1788 H H H Me 2 —(CH2)3—O-(4-Ac—Ph) H H
1-1789 H H H Me 2 —(CH2)4—O-(3,4-diF—Ph) H H
1-1790 H H H Me 2 —(CH2)4—O-(3,5-diF—Ph) H H
1-1791 H H H Me 2 —(CH2)4—O-(3,4-diMeo—Ph) H H
1-1792 H H H Me 2 —(CH2)4—O-(3,5-diMeo—Ph) H H
1-1793 H H H Me 2 —(CH2)4—O-(3,4,5-triMeO—Ph) H H
1-1794 H H H Me 2 —(CH2)4—O-(3-Ac—Ph) H H
1-1795 H H H Me 2 —(CH2)4—O-(4-Ac—Ph) H H
1-1796 H H H Me 2 —C≡C—(CH2)2-(3-F—Ph) H H
1-1797 H H H Me 2 —C≡C—(CH2)2-(3,4-diF—Ph) H H
1-1798 H H H Me 2 —C≡C—(CH2)2-(3,5-diF—Ph) H H
1-1799 H H H Me 2 —C≡C—(CH2)2-(3-Cl—Ph) H H
1-1800 H H H Me 2 —C≡C—(CH2)2-(4-Cl—Ph) H H
1-1801 H H H Me 2 —C≡C—(CH2)2-(3,4-diCl—Ph) H H
1-1802 H H H Me 2 —C≡C—(CH2)2-(3,5-diCl—Ph) H H
1-1803 H H H Me 2 —C≡C—(CH2)2-(3-Me—Ph) H H
1-1804 H H H Me 2 —C≡C—(CH2)2-(3,4-diMe—Ph) H H
1-1805 H H H Me 2 —C≡C—(CH2)2-(3,5-diMe—Ph) H H
1-1806 H H H Me 2 —C≡C—(CH2)2-(3-CF3—Ph) H H
1-1807 H H H Me 2 —C≡C—(CH2)2-(3,4-diCF3—Ph) H H
1-1808 H H H Me 2 —C≡C—(CH2)2-(3,5-diCF3—Ph) H H
1-1809 H H H Me 2 —C≡C—(CH2)2-(3-MeO—Ph) H H
1-1810 H H H Me 2 —C≡C—(CH2)2-(3,4-diMeO—Ph) H H
1-1811 H H H Me 2 —C≡C—(CH2)2-(3,5-diMeO—Ph) H H
1-1812 H H H Me 2 —C≡C—(CH2)2-(3,4,5-triMeO—Ph) H H
1-1813 H H H Me 2 —C≡C—(CH2)2-(3-Ac—Ph) H H
1-1814 H H H Me 2 —C≡C—(CH2)2-(4-Ac—Ph) H H
1-1815 H H H Me 2 —C≡C—(CH2)3-(3,4-diF—Ph) H H
1-1816 H H H Me 2 —C≡C—(CH2)3-(3,5-diF—Ph) H H
1-1817