CA2248800A1 - Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders - Google Patents
Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disordersInfo
- Publication number
- CA2248800A1 CA2248800A1 CA002248800A CA2248800A CA2248800A1 CA 2248800 A1 CA2248800 A1 CA 2248800A1 CA 002248800 A CA002248800 A CA 002248800A CA 2248800 A CA2248800 A CA 2248800A CA 2248800 A1 CA2248800 A1 CA 2248800A1
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen
- defined above
- group
- compounds
- independently selected
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C313/08—Sulfenic acids; Derivatives thereof
- C07C313/18—Sulfenamides
- C07C313/36—Sulfenamides having nitrogen atoms of sulfenamide groups further bound to other hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/0026—Oxygen-containing hetero ring cyclic ketals
- C07J71/0031—Oxygen-containing hetero ring cyclic ketals at positions 16, 17
Abstract
Disclosed are (i) compounds of a steroid, a .beta.-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, .beta.-agonists, anticholinergics, mast cell stabilizers and PDE
inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO-), or as the neutral species, nitric oxide (NO) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO-), or as the neutral species, nitric oxide (NO) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
Claims (16)
1. A compound comprising a steroid, a .beta.-agonist, an anticholinergic, a mast cell stabilizer or a phosphodiesterase inhibitor to which is directly or indirectly linked at least one NO or NO2 group or a group which stimulates endogenous production of NO or EDRF synthesis in vivo.
2. A compounds of claim 1 selected from the group consisting of:
(i) compounds having the structure:
wherein A is selected from -CH=CH- or -CH2-CH2-;
R1 is selected from (1) -C(O)CH2-B-D wherein B is oxygen or sulfur; D is selected from (i) -NO; (ii) -NO2; (iii) -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q in which R d is hydrogen, lower alkyl, cycloalkyl, aryl, alkylaryl, aryl or heteroaryl, Y is oxygen, sulfur, or NR i in which R i is hydrogen, lower alkyl, lower haloalkyl, or heteroaryl, R e and R f are at each occurance independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, alkylamino, dialkylamino, carboxy, carboxamido, or taken together are carbonyl, cycloalkyl or bridged cycloalkyl, p is an integer from 1 to 6, T is a covalent bond, oxygen, sulfur or nitrogen and Q is selected from -NO or -NO2; (iv) -C(O)-T1-[C(R e)(R f)]p-T2-Q wherein T1 and T2 are independently selected from T and R e, R f, p, Q, and T are as defined above; (v) -C(O)-T[C(R y)(R z)]p wherein R y and R z are independently selected from -T1-[C(R e)(R f)]p-G-[C(R e)(R f)]p-T2-Q wherein G is (i) a covalent bond; (ii) -T-C(O)-; (iii) -C(O)-T, or (iv) Y, and wherein R d, R e, R f, p, Q, T, and Y are as defined above;
(2) -C(O)-C(O)-O-R i wherein R i is as defined above;
(3) -C(O)-B-R i wherein B and R i are as defined above;
(4) -C(O)-CH2-B-C(O)-R i wherein B and R i are as defined above;
(5) -C(O)-CH2-X wherein X is halogen;
(6) -S-R i wherein R i is as defined above;
(7) -C(O)CH2-B-M wherein M is selected from -C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]-R i or -C(R d)-O-C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherein Re, Rf, Ri, p, G and T are as defined above;
R2 and R3 are independently selected from hydrogen, hydroxyl, lower alkyl, -O(O)C-R i, or -S-R i wherein R i is as defined above or R2 and R3 when taken together are wherein R1 i and R2 i are independently selected from R i wherein R i is as defined above;
R4 and R5 are independently selected from hydrogen or halogen;
R6 is selected from hydrogen, D, or M wherein D and M are as defined above with the provision that R6 must be D or M if the selection for R1 does not include D or M;
(ii) compounds having the structure:
wherein, E is nitrogen or C-R7 wherein R7 is hydrogen, halogen, -CH2O-R j, or -O-R j wherein R j is hydrogen, D or M wherein D and M are defined as above;
R8 and R9 are independently selected from amino, hydrogen, -CH2O-R j, or -O-R k wherein R k is -C(O)- R d or R j and R d and R j are as defined above;
S is (1) -CH2-N(Z)-R10 wherein Z is hydrogen, -[N(O-)N=O], or M wherein M is as defined above and R10 is selected from (i) lower alkyl (ii) -(CH2)p-O-(CH2)a-C6H5 wherein a is an integer from 1 to 4 and p is as defined above (iii) wherein Z is as defined above; and R11 is selected from hydrogen, D, or M with the provision that R11 must be D
or M if neither R8 or R9 include D or M and Z is hydrogen;
(iii) compounds having the structure:
wherein, K is a a monovalent anion selected from halide, nitrate, or nitrite;
R12 and R13 are hydrogen or, when taken together are oxygen;
R14 is lower alkyl or haloalkyl;
R15 is selected from:
wherein R v is selected from D or M and D and M are as defined above;
(iv) compounds having the structure:
wherein R14 is as defined above;
R16 is selected from hydrogen, -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q, -C(O)-T1-[C(R e)(R f)]p-T2-Q, or M; and wherein R d, R e, R f,, M, p, T, T1, T2, Q, and Y are defined as above; and R17 and R18 are independently selected from a lone pair of electrons, -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q, or M wherein R d, R e, R f,, M, p, T, Q, and Y are defined as above with the provision that R17 and/or R18 must be -C(R d)-O-C(O)- Y-[C(R e)(R f)]p-T-Q or M when R16 is hydrogen;
(v) compounds having the structure:
wherein R19 is selected from -[C(R e)(R f)]p-G-[C(R e)(R f)]p-T-Q or -S(O2)-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R j wherein R e, R f, R i, p, G, Q and T are as defined above; and wherein R14, R17, and R18 are as defined above;
(vi) compounds having the structure:
wherein, F is selected from oxygen or NR i wherein R i is as defined above;
R20 and R21 are independently selected from (1) -Y-[C(R e)(R f)]p-H-[C(R e)(R f)]p- T-Q; wherein H is (i) a covalent bond; (ii) -T-C(O)-; (iii) -C(O)-T;
(iv) -C(Y-C(O)-R m)- wherein R m is heteroaryl or heterocyclic ring; and wherin Y, R d, R e, R f, p, Q and T are as defined above; (2) T-[C(R e)(R f)]p-H-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherin R d, R e, R f, R i, p, H and T are as defined above; (3) in which W is a heterocyclic ring or NR s R's wherein R s and R's are independently selected from lower alkyl, aryl or alkenyl; (4) sodium or (5) hydrogen;
R22 is hydrogen, M, or D with the provision that R22 must be M or D when R20 and R21 are selected as sodium or hydrogen;
(vii) compounds having the structure:
wherein, R23 is alkoxy, cycloalkoxy, or halogen;
R24 is hydrogen, alkoxy, or haloalkoxy; and R25 is selected from:
wherein X is halogen and R26 is selected from D or M and wherein R16, R18, and R19 are defined as above.
(i) compounds having the structure:
wherein A is selected from -CH=CH- or -CH2-CH2-;
R1 is selected from (1) -C(O)CH2-B-D wherein B is oxygen or sulfur; D is selected from (i) -NO; (ii) -NO2; (iii) -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q in which R d is hydrogen, lower alkyl, cycloalkyl, aryl, alkylaryl, aryl or heteroaryl, Y is oxygen, sulfur, or NR i in which R i is hydrogen, lower alkyl, lower haloalkyl, or heteroaryl, R e and R f are at each occurance independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, alkylamino, dialkylamino, carboxy, carboxamido, or taken together are carbonyl, cycloalkyl or bridged cycloalkyl, p is an integer from 1 to 6, T is a covalent bond, oxygen, sulfur or nitrogen and Q is selected from -NO or -NO2; (iv) -C(O)-T1-[C(R e)(R f)]p-T2-Q wherein T1 and T2 are independently selected from T and R e, R f, p, Q, and T are as defined above; (v) -C(O)-T[C(R y)(R z)]p wherein R y and R z are independently selected from -T1-[C(R e)(R f)]p-G-[C(R e)(R f)]p-T2-Q wherein G is (i) a covalent bond; (ii) -T-C(O)-; (iii) -C(O)-T, or (iv) Y, and wherein R d, R e, R f, p, Q, T, and Y are as defined above;
(2) -C(O)-C(O)-O-R i wherein R i is as defined above;
(3) -C(O)-B-R i wherein B and R i are as defined above;
(4) -C(O)-CH2-B-C(O)-R i wherein B and R i are as defined above;
(5) -C(O)-CH2-X wherein X is halogen;
(6) -S-R i wherein R i is as defined above;
(7) -C(O)CH2-B-M wherein M is selected from -C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]-R i or -C(R d)-O-C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherein Re, Rf, Ri, p, G and T are as defined above;
R2 and R3 are independently selected from hydrogen, hydroxyl, lower alkyl, -O(O)C-R i, or -S-R i wherein R i is as defined above or R2 and R3 when taken together are wherein R1 i and R2 i are independently selected from R i wherein R i is as defined above;
R4 and R5 are independently selected from hydrogen or halogen;
R6 is selected from hydrogen, D, or M wherein D and M are as defined above with the provision that R6 must be D or M if the selection for R1 does not include D or M;
(ii) compounds having the structure:
wherein, E is nitrogen or C-R7 wherein R7 is hydrogen, halogen, -CH2O-R j, or -O-R j wherein R j is hydrogen, D or M wherein D and M are defined as above;
R8 and R9 are independently selected from amino, hydrogen, -CH2O-R j, or -O-R k wherein R k is -C(O)- R d or R j and R d and R j are as defined above;
S is (1) -CH2-N(Z)-R10 wherein Z is hydrogen, -[N(O-)N=O], or M wherein M is as defined above and R10 is selected from (i) lower alkyl (ii) -(CH2)p-O-(CH2)a-C6H5 wherein a is an integer from 1 to 4 and p is as defined above (iii) wherein Z is as defined above; and R11 is selected from hydrogen, D, or M with the provision that R11 must be D
or M if neither R8 or R9 include D or M and Z is hydrogen;
(iii) compounds having the structure:
wherein, K is a a monovalent anion selected from halide, nitrate, or nitrite;
R12 and R13 are hydrogen or, when taken together are oxygen;
R14 is lower alkyl or haloalkyl;
R15 is selected from:
wherein R v is selected from D or M and D and M are as defined above;
(iv) compounds having the structure:
wherein R14 is as defined above;
R16 is selected from hydrogen, -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q, -C(O)-T1-[C(R e)(R f)]p-T2-Q, or M; and wherein R d, R e, R f,, M, p, T, T1, T2, Q, and Y are defined as above; and R17 and R18 are independently selected from a lone pair of electrons, -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q, or M wherein R d, R e, R f,, M, p, T, Q, and Y are defined as above with the provision that R17 and/or R18 must be -C(R d)-O-C(O)- Y-[C(R e)(R f)]p-T-Q or M when R16 is hydrogen;
(v) compounds having the structure:
wherein R19 is selected from -[C(R e)(R f)]p-G-[C(R e)(R f)]p-T-Q or -S(O2)-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R j wherein R e, R f, R i, p, G, Q and T are as defined above; and wherein R14, R17, and R18 are as defined above;
(vi) compounds having the structure:
wherein, F is selected from oxygen or NR i wherein R i is as defined above;
R20 and R21 are independently selected from (1) -Y-[C(R e)(R f)]p-H-[C(R e)(R f)]p- T-Q; wherein H is (i) a covalent bond; (ii) -T-C(O)-; (iii) -C(O)-T;
(iv) -C(Y-C(O)-R m)- wherein R m is heteroaryl or heterocyclic ring; and wherin Y, R d, R e, R f, p, Q and T are as defined above; (2) T-[C(R e)(R f)]p-H-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherin R d, R e, R f, R i, p, H and T are as defined above; (3) in which W is a heterocyclic ring or NR s R's wherein R s and R's are independently selected from lower alkyl, aryl or alkenyl; (4) sodium or (5) hydrogen;
R22 is hydrogen, M, or D with the provision that R22 must be M or D when R20 and R21 are selected as sodium or hydrogen;
(vii) compounds having the structure:
wherein, R23 is alkoxy, cycloalkoxy, or halogen;
R24 is hydrogen, alkoxy, or haloalkoxy; and R25 is selected from:
wherein X is halogen and R26 is selected from D or M and wherein R16, R18, and R19 are defined as above.
3. A composition comprising (i) a therapeutically effective amount of a steroid, a .beta.-agonist, an anticholinergic, a mast cell stabilizer or a PDE inhibitor and (ii) a compound that donates, transfers or releases nitric oxide or stimulates endogenous production of NO or EDRF in vivo.
4. The composition of claim 3 wherein (i) the steroid is selected from the group consisting of beclomethasone, fluticasone, flunisolide, triamcinolone, butixocort, dexamethasone, fluocortin, budesonide, tixocortol, tipredane and mometasone;
(ii) the .beta.-agonist is selected from the group consisting of salmeterol, albuterol, metaproternol, terbutaline, pirbuterol, rimiterol, clenbuterol, bitolterol and reproterol;
(iii) the anticholinergic is selected form the group consisting of ipratrupium, flutropium, tiotropium and rispenzepine;
(iv) the mast cell stabilizer is selected from the group consisting of cromolyn and nedocromil; and (v) the PDE inhibitor is selected from the group consisting of tolafentrine, piclamilast, rolipram, filaminast, denbufylline, and zardaverine.
(ii) the .beta.-agonist is selected from the group consisting of salmeterol, albuterol, metaproternol, terbutaline, pirbuterol, rimiterol, clenbuterol, bitolterol and reproterol;
(iii) the anticholinergic is selected form the group consisting of ipratrupium, flutropium, tiotropium and rispenzepine;
(iv) the mast cell stabilizer is selected from the group consisting of cromolyn and nedocromil; and (v) the PDE inhibitor is selected from the group consisting of tolafentrine, piclamilast, rolipram, filaminast, denbufylline, and zardaverine.
5. The composition of claim 3 wherein the compound that donates, transfers or releases nitric oxide is a S-nitrosothiol.
6. The composition of claim 5 wherein the S-nitrosothiol is selected from the group consisting of those having the structures:
(i) CH3[C(R e)(R f)]x SNO;
(ii) HS[C(R e)(R f)]x SNO;
(iii) ONS[C(R e)(R f)x B; and (iv) H2N-(CO2H)-(CH2)x-C(O)NH-C(CH2SNO)-C(O)NH-CH2-CO2H
wherein x equals 2 to 20; R e and R f are independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, hereroaryl, arylalkyl, alkylamino, dialkylamino or taken together are carbonyl, cycloalkyl or bridged cycloalkyl; and B is selectedfrom the group consisting of fluoro, alkoxy, cyano, carboxamido, cycloalkyl, arylkoxy, alkylsulfinyl, arylthio, alkylamino, dialkylamino, hydroxy, carbamoyl,N-alkylcarbamoyl, N,N-dialkylcarbamoyl, amino, hydroxyl, carboxyl, hydrogen, nitro and aryl.
(i) CH3[C(R e)(R f)]x SNO;
(ii) HS[C(R e)(R f)]x SNO;
(iii) ONS[C(R e)(R f)x B; and (iv) H2N-(CO2H)-(CH2)x-C(O)NH-C(CH2SNO)-C(O)NH-CH2-CO2H
wherein x equals 2 to 20; R e and R f are independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, hereroaryl, arylalkyl, alkylamino, dialkylamino or taken together are carbonyl, cycloalkyl or bridged cycloalkyl; and B is selectedfrom the group consisting of fluoro, alkoxy, cyano, carboxamido, cycloalkyl, arylkoxy, alkylsulfinyl, arylthio, alkylamino, dialkylamino, hydroxy, carbamoyl,N-alkylcarbamoyl, N,N-dialkylcarbamoyl, amino, hydroxyl, carboxyl, hydrogen, nitro and aryl.
7. The composition of claim 3 wherein the compound that donates, transfers or releases nitric oxide is selected from the group consisting of:
(i) compounds that include at least one ON-O-, ON-N- or ON-C- group;
(ii) a 2-hydroxy-2-nitrosohydrazine which has an R61R62-N(O-M+)-NO group wherein R61 and R62 include polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, hydrocarbons where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or anaromatic hydrocarbon, hydrocarbons having one or more substituent groups and heterocyclic compounds;
(iii) a thionitrate which has the structure R70-S-NO2 wherein R10 includes polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, anda hydrocarbon where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or an aromatic hydrocarbon; and (iv) a nitrate which has the structure R70-O-NO2 wherein R70 is as defined above.
(i) compounds that include at least one ON-O-, ON-N- or ON-C- group;
(ii) a 2-hydroxy-2-nitrosohydrazine which has an R61R62-N(O-M+)-NO group wherein R61 and R62 include polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, hydrocarbons where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or anaromatic hydrocarbon, hydrocarbons having one or more substituent groups and heterocyclic compounds;
(iii) a thionitrate which has the structure R70-S-NO2 wherein R10 includes polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, anda hydrocarbon where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or an aromatic hydrocarbon; and (iv) a nitrate which has the structure R70-O-NO2 wherein R70 is as defined above.
8. The composition of claim 3 wherein the compound that stimulates the endogenous production of NO or EDRF in vivo is selected from the group consisting of L-arginine, cytokines, adenosine, bradykinin, calreticulin, bisacodyl, phenolphthalein and endothelein.
9. A composition comprising (i) a compound selected from the group consisting of a steroid, a .beta.-agonist, an anticholinergic, a mast cell stabilizer and a PDE inhibitor to which is directly or indirectly linked at least one nitro or nitroso group or a group which stimulates endogenous synthesis of NO or EDRF in vivo and (ii) a compound that donates, transfers or releases nitric oxide or elevatesendogenous synthesis levels of nitric oxide.
10. The composition of claim 9 wherein the steroid, .beta.-agonist, anticholinergic, mast cell stabilizer or PDE inhibitor is a compound which has been linked through a site selected from the group consisting of oxygen, sulfur, carbon and nitrogen.
11. The composition of claim 9 wherein compound (i) is selected from the group consisting of:
(i) compounds having the structure:
wherein A is selected from -CH=CH- or-CH2-CH2-;
R1 is selected from (1) -C(O)CH2-B-D wherein B is oxygen or sulfur; D is selected from (i) -NO; (ii) -NO2; (iii) -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q in which R d is hydrogen, lower alkyl, cycloalkyl, aryl, alkylaryl, aryl or heteroaryl, Y is oxygen, sulfur, or NR i in which R i is hydrogen, lower alkyl, lower haloalkyl, or heteroaryl, R e and R f are at each occurance independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, alkylamino, dialkylamino, carboxy, carboxamido, or taken together are carbonyl, cycloalkyl or bridged cycloalkyl, pis an integer from 1 to 6, T is a covalent bond, oxygen, sulfur or nitrogen and Q is selected from -NO or -NO2; (iv) -C(O)-T1-[C(R e)(R f)]p-T2-Q wherein T1 and T2 are independently selected from T and R e, R f, p, Q, and T are as defined above;
(v) -C(O)-T[C(R y)(R z)]p wherein R y and R z are independently selected from -T1-[C(R e)(R f)]p-G-[C(R e)(R f)]p-T2-Q wherein G is (i) a covalent bond; (ii) -T-C(O)-;
(iii) -C(O)-T, or (iv) Y, and wherein R d, R e, R f, p, Q, T, and Y are as defined above;
(2) -C(O)-C(O)-O-R i wherein R i is as defined above;
(3) -C(O)-B-R i wherein B and R i are as defined above;
(4) -C(O)-CH2-B-C(O)-R i wherein B and R i are as defined above;
(5) -C(O)-CH2-X wherein X is halogen;
(6) -S-R i wherein R i is as defined above;
(7) -C(O)CH2-B-M wherein M is selected from -C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R i or -C(R d)-O-C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]-R i wherein R e, R f, R i, p, G and T are as defined above;
R2 and R3 are independently selected from hydrogen, hydroxyl, lower alkyl, -O(O)C-R i, or -S-R i wherein R i is as defined above or R2 and R3 when taken together are wherein R1; and R2; are independently selected from R i wherein R i is as defined above;
R4 and R5 are independently selected from hydrogen or halogen;
R6 is selected from hydrogen, D, or M wherein D and M are as defined above with the provision that R6 must be D or M if the selection for R1 does not include D or M;
(ii) compounds having the structure:
wherein, E is nitrogen or C-R7 wherein R7 is hydrogen, halogen, -CH2O-R j, or -O-R j wherein R j is hydrogen, D or M wherein D and M are defined as above;
R8 and R9 are independently selected from amino, hydrogen, -CH2O-R j, or -O-R k, wherein R k is -C(O)- R d or R j and R d and R j are as defined above;
S is (1) -CH2-N(Z)-R10 wherein Z is hydrogen, -[N(O-)N=O], or M wherein M is as defined above and R10 is selected from (i) lower alkyl (ii) -(CH2)p-O-(CH2)a-C6H5 wherein a is an integer from 1 to 4 and p is as defined above;
wherein Z is as defined above; and R11 is selected from hydrogen, D, or M with the provision that R11 must be D
or M if neither R8 or R9 include D or M and Z is hydrogen;
(iii) compounds having the structure:
wherein, K is a a monovalent anion selected from halide, nitrate, or nitrite;
R12 and R13 are hydrogen or, when taken together are oxygen;
R14 is lower alkyl or haloalkyl;
R15 is selected from:
wherein R v is selected from D or M and D and M are as defined above;
(iv) compounds having the structure:
wherein R14 is as defined above;
R16 is selected from hydrogen, -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q, -C(O)-T1-[C(R e)(R f)]p- T2-Q, or M; and wherein R d, R e, R f,, M, p, T, T1, T2, Q, and Y are defined as above; and R17 and R18 are independently selected from a lone pair of electrons, -C(R d)-O- C(O)-Y-[C(R e)(R f)]p-T-Q, or M wherein R d, R e, R f,, M, p, T, Q, and Y are defined as above with the provision that R17 and/or R18 must be -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q or M when R16 is hydrogen;
(v) compounds having the structure:
wherein R19 is selected from -[C(R e)(R f)]p-G-[C(R e)(R f)]p-T-Q or -S(O2)-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherein R e, R f, R i, p, G, Q and T are as defined above; and wherein R14, R17, and R18 are as defined above;
(vi) compounds having the structure:
wherein, F is selected from oxygen or NR i wherein R i is as defined above;
R20 and R21 are independently selected from (1) -Y-[C(R e)(R f)]p-H-[C(R e)(R f)]p- T-Q; wherein H is (i) a covalent bond; (ii) -T-C(O)-; (iii) -C(O)-T;
(iv) -C(Y-C(O)-R m)- wherein R m is heteroaryl or heterocyclic ring; and wherin Y, R d, R e, R f, p, Q and T are as defined above; (2) T-[C(R e)(R f)]p-H-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherin R d, R e, R f, R i, p, H and T are as defined above; (3) in which W is a heterocyclic ring or NR s R's wherein R s and R's are independently selected from lower alkyl, aryl or alkenyl; (4) sodium or (5) hydrogen;
R22 is hydrogen, M, or D with the provision that R22 must be M or D when R20 and R21 are selected as sodium or hydrogen;
(vii) compounds having the structure:
wherein, R23 is alkoxy, cycloalkoxy, or halogen;
R24 is hydrogen, alkoxy, or haloalkoxy; and R25 is selected from:
wherein X is halogen and R26 is selected from D or M and wherein R16, R18, and R19 are defined as above.
(i) compounds having the structure:
wherein A is selected from -CH=CH- or-CH2-CH2-;
R1 is selected from (1) -C(O)CH2-B-D wherein B is oxygen or sulfur; D is selected from (i) -NO; (ii) -NO2; (iii) -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q in which R d is hydrogen, lower alkyl, cycloalkyl, aryl, alkylaryl, aryl or heteroaryl, Y is oxygen, sulfur, or NR i in which R i is hydrogen, lower alkyl, lower haloalkyl, or heteroaryl, R e and R f are at each occurance independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, alkylamino, dialkylamino, carboxy, carboxamido, or taken together are carbonyl, cycloalkyl or bridged cycloalkyl, pis an integer from 1 to 6, T is a covalent bond, oxygen, sulfur or nitrogen and Q is selected from -NO or -NO2; (iv) -C(O)-T1-[C(R e)(R f)]p-T2-Q wherein T1 and T2 are independently selected from T and R e, R f, p, Q, and T are as defined above;
(v) -C(O)-T[C(R y)(R z)]p wherein R y and R z are independently selected from -T1-[C(R e)(R f)]p-G-[C(R e)(R f)]p-T2-Q wherein G is (i) a covalent bond; (ii) -T-C(O)-;
(iii) -C(O)-T, or (iv) Y, and wherein R d, R e, R f, p, Q, T, and Y are as defined above;
(2) -C(O)-C(O)-O-R i wherein R i is as defined above;
(3) -C(O)-B-R i wherein B and R i are as defined above;
(4) -C(O)-CH2-B-C(O)-R i wherein B and R i are as defined above;
(5) -C(O)-CH2-X wherein X is halogen;
(6) -S-R i wherein R i is as defined above;
(7) -C(O)CH2-B-M wherein M is selected from -C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R i or -C(R d)-O-C(O)T-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]-R i wherein R e, R f, R i, p, G and T are as defined above;
R2 and R3 are independently selected from hydrogen, hydroxyl, lower alkyl, -O(O)C-R i, or -S-R i wherein R i is as defined above or R2 and R3 when taken together are wherein R1; and R2; are independently selected from R i wherein R i is as defined above;
R4 and R5 are independently selected from hydrogen or halogen;
R6 is selected from hydrogen, D, or M wherein D and M are as defined above with the provision that R6 must be D or M if the selection for R1 does not include D or M;
(ii) compounds having the structure:
wherein, E is nitrogen or C-R7 wherein R7 is hydrogen, halogen, -CH2O-R j, or -O-R j wherein R j is hydrogen, D or M wherein D and M are defined as above;
R8 and R9 are independently selected from amino, hydrogen, -CH2O-R j, or -O-R k, wherein R k is -C(O)- R d or R j and R d and R j are as defined above;
S is (1) -CH2-N(Z)-R10 wherein Z is hydrogen, -[N(O-)N=O], or M wherein M is as defined above and R10 is selected from (i) lower alkyl (ii) -(CH2)p-O-(CH2)a-C6H5 wherein a is an integer from 1 to 4 and p is as defined above;
wherein Z is as defined above; and R11 is selected from hydrogen, D, or M with the provision that R11 must be D
or M if neither R8 or R9 include D or M and Z is hydrogen;
(iii) compounds having the structure:
wherein, K is a a monovalent anion selected from halide, nitrate, or nitrite;
R12 and R13 are hydrogen or, when taken together are oxygen;
R14 is lower alkyl or haloalkyl;
R15 is selected from:
wherein R v is selected from D or M and D and M are as defined above;
(iv) compounds having the structure:
wherein R14 is as defined above;
R16 is selected from hydrogen, -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q, -C(O)-T1-[C(R e)(R f)]p- T2-Q, or M; and wherein R d, R e, R f,, M, p, T, T1, T2, Q, and Y are defined as above; and R17 and R18 are independently selected from a lone pair of electrons, -C(R d)-O- C(O)-Y-[C(R e)(R f)]p-T-Q, or M wherein R d, R e, R f,, M, p, T, Q, and Y are defined as above with the provision that R17 and/or R18 must be -C(R d)-O-C(O)-Y-[C(R e)(R f)]p-T-Q or M when R16 is hydrogen;
(v) compounds having the structure:
wherein R19 is selected from -[C(R e)(R f)]p-G-[C(R e)(R f)]p-T-Q or -S(O2)-[C(R e)(R f)]p-G-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherein R e, R f, R i, p, G, Q and T are as defined above; and wherein R14, R17, and R18 are as defined above;
(vi) compounds having the structure:
wherein, F is selected from oxygen or NR i wherein R i is as defined above;
R20 and R21 are independently selected from (1) -Y-[C(R e)(R f)]p-H-[C(R e)(R f)]p- T-Q; wherein H is (i) a covalent bond; (ii) -T-C(O)-; (iii) -C(O)-T;
(iv) -C(Y-C(O)-R m)- wherein R m is heteroaryl or heterocyclic ring; and wherin Y, R d, R e, R f, p, Q and T are as defined above; (2) T-[C(R e)(R f)]p-H-[C(R e)(R f)]p-N[N-(O-)N=O]- R i wherin R d, R e, R f, R i, p, H and T are as defined above; (3) in which W is a heterocyclic ring or NR s R's wherein R s and R's are independently selected from lower alkyl, aryl or alkenyl; (4) sodium or (5) hydrogen;
R22 is hydrogen, M, or D with the provision that R22 must be M or D when R20 and R21 are selected as sodium or hydrogen;
(vii) compounds having the structure:
wherein, R23 is alkoxy, cycloalkoxy, or halogen;
R24 is hydrogen, alkoxy, or haloalkoxy; and R25 is selected from:
wherein X is halogen and R26 is selected from D or M and wherein R16, R18, and R19 are defined as above.
12. The composition of claim 9 wherein (i) the steroid is selected from the group consisting of beclomethasone, fluticasone, flunisoloide, triamicnolone, butixocort, dexamethasone, fluocortin,budesonide, tixocortol, tipredane and mometasone;
(ii) the .beta.-agonist is selected from the group consisting of salmeterol, albuterol, metaproternol, terbutaline, pirbuterol, clenbuterol, bitolterol and reproterol;
(iii) the anticholinergic is selected form the group consisting of ipratropium, flutropium, tiotropium and rispenzepine;
(iv) the mast cell stabilizer is selected from the group consisting of cromolyn and nedocromyl; and (v) the PDE inhibitor is selected from the group consisting of filaminast, denbufyllene, piclamilast, zardaverine and rolipram.
(ii) the .beta.-agonist is selected from the group consisting of salmeterol, albuterol, metaproternol, terbutaline, pirbuterol, clenbuterol, bitolterol and reproterol;
(iii) the anticholinergic is selected form the group consisting of ipratropium, flutropium, tiotropium and rispenzepine;
(iv) the mast cell stabilizer is selected from the group consisting of cromolyn and nedocromyl; and (v) the PDE inhibitor is selected from the group consisting of filaminast, denbufyllene, piclamilast, zardaverine and rolipram.
13. The composition of claim 9 wherein the compound that donates, transfers or releases nitric oxide is a S-nitrosothiol.
14. The composition of claim 13 wherein the S-nitrosothiol is selected from the group consisting of those having the structures:
(i) CH3[C(R e)(R f)]x SNO;
(ii) HS[C(R e)(R f)]x SNO;
(iii) ONS[C(R e)(R f)]x B; and (iv) H2N-(CO2H)-(CH2)x-C(O)NH-C(CH2SNO)-C(O)NH-CH2-CO2H
wherein x equals 2 to 20; R e and R f are independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, hereroaryl, arylalkyl, alkylamino, dialkylamino or taken together are carbonyl, cycloalkyl or bridged cycloalkyl; and B is selectedfrom the group consisting of fluoro, alkoxy, cyano, carboxamido, cycloalkyl, arylkoxy, alkylsulfinyl, arylthio, alkylamino, dialkylamino, hydroxy, carbamoyl,N-alkylcarbamoyl, N,N-dialkylcarbamoyl, amino, hydroxyl, carboxyl, hydrogen, nitro and aryl.
(i) CH3[C(R e)(R f)]x SNO;
(ii) HS[C(R e)(R f)]x SNO;
(iii) ONS[C(R e)(R f)]x B; and (iv) H2N-(CO2H)-(CH2)x-C(O)NH-C(CH2SNO)-C(O)NH-CH2-CO2H
wherein x equals 2 to 20; R e and R f are independently selected from hydrogen, lower alkyl, cycloalkyl, aryl, hereroaryl, arylalkyl, alkylamino, dialkylamino or taken together are carbonyl, cycloalkyl or bridged cycloalkyl; and B is selectedfrom the group consisting of fluoro, alkoxy, cyano, carboxamido, cycloalkyl, arylkoxy, alkylsulfinyl, arylthio, alkylamino, dialkylamino, hydroxy, carbamoyl,N-alkylcarbamoyl, N,N-dialkylcarbamoyl, amino, hydroxyl, carboxyl, hydrogen, nitro and aryl.
15. The composition of claim 13 wherein the compound that donates, transfers or releases nitric oxide is selected from the group consisting of:
(i) compounds that include at least one ON-O-, ON-N- or ON-C- group;
(ii) a N-oxo-N-nitrosoamine which has an R61R62-N(O-M+)-NO group wherein R61 and R62 include polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, hydrocarbons where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or anaromatic hydrocarbon, hydrocarbons having one or more substituent groups and heterocyclic compounds; and (iii) a thionitrate which has the structure R70-S-NO2 wherein R70 includes polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, anda hydrocarbon where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or an aromatic hydrocarbon; and (iv) a nitrate which has the structure R70-O-NO2 wherein R70 is as defined above.
(i) compounds that include at least one ON-O-, ON-N- or ON-C- group;
(ii) a N-oxo-N-nitrosoamine which has an R61R62-N(O-M+)-NO group wherein R61 and R62 include polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, hydrocarbons where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or anaromatic hydrocarbon, hydrocarbons having one or more substituent groups and heterocyclic compounds; and (iii) a thionitrate which has the structure R70-S-NO2 wherein R70 includes polypeptides, amino acids, sugars, modified and unmodified oligonucleotides, anda hydrocarbon where the hydrocarbon can be a branched or unbranched, and saturated or unsaturated aliphatic hydrocarbon or an aromatic hydrocarbon; and (iv) a nitrate which has the structure R70-O-NO2 wherein R70 is as defined above.
16. The composition of claim 9 wherein the compound that stimulates the endogenous production of NO or EDRF in vivo is selected from the group consisting of L-arginine, cytokines, adenosine, bradykinin, calreticulin, bisacodyl, phenolphthalein, and endothelein.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/620,882 | 1996-03-22 | ||
US08/620,882 US5824669A (en) | 1996-03-22 | 1996-03-22 | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
PCT/US1997/004319 WO1997034871A1 (en) | 1996-03-22 | 1997-03-19 | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2248800A1 true CA2248800A1 (en) | 1997-09-25 |
CA2248800C CA2248800C (en) | 2012-02-21 |
Family
ID=24487809
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2248800A Expired - Fee Related CA2248800C (en) | 1996-03-22 | 1997-03-19 | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
Country Status (6)
Country | Link |
---|---|
US (6) | US5824669A (en) |
EP (1) | EP0904266A4 (en) |
JP (1) | JP2000509016A (en) |
AU (1) | AU733202B2 (en) |
CA (1) | CA2248800C (en) |
WO (1) | WO1997034871A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009037584A2 (en) * | 2007-08-10 | 2009-03-26 | Topigen Pharmaceuticals Inc. | Combination of nitroderivatized steroid and bronchodilator for treating respiratory disease |
WO2009071990A2 (en) * | 2007-08-31 | 2009-06-11 | Topigen Pharmaceuticals Inc. | No-donating cordicosteroid with improved pharmacokinetic, anti-inflammatory and vasodilatory properties |
Families Citing this family (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5824669A (en) * | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
IT1285770B1 (en) * | 1996-10-04 | 1998-06-18 | Nicox Sa | CORTICOID COMPOUNDS |
WO1998019672A1 (en) * | 1996-11-01 | 1998-05-14 | Nitromed Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
US6331543B1 (en) | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
US5958926A (en) * | 1996-11-01 | 1999-09-28 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
USRE37234E1 (en) | 1996-11-01 | 2001-06-19 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiestrase inhibitor compounds, compositions and their uses |
US6472425B1 (en) | 1997-10-31 | 2002-10-29 | Nitromed, Inc. | Methods for treating female sexual dysfunctions |
GB9801398D0 (en) | 1998-01-22 | 1998-03-18 | Anggard Erik E | Chemical compounds |
US6667299B1 (en) * | 2000-03-16 | 2003-12-23 | Hollis-Eden Pharmaceuticals, Inc. | Pharmaceutical compositions and treatment methods |
FR2786699B1 (en) * | 1998-12-02 | 2002-10-04 | Philippe Gorny | MEDICINE, IN PARTICULAR FOR PREVENTING OR TREATING SEXUAL DYSFUNCTIONS |
AU3703900A (en) * | 1999-02-24 | 2000-09-14 | Nitromed, Inc. | Nitrosated and nitrosylated steroids for the treatment of cardiovascular diseases and disorders |
US7176238B1 (en) * | 1999-03-01 | 2007-02-13 | Nitromed Inc. | Nitrostated and nitrosylated prostaglandins, compositions and methods of use |
DE19921693A1 (en) | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Pharmaceutical composition for treating respiratory disorders, e.g. asthma, comprises combination of anticholinergic and beta-mimetic agents having synergistic bronchospasmolytic activity and reduced side-effects |
US20100197719A1 (en) * | 1999-05-12 | 2010-08-05 | Boehringer Ingelheim Pharma Kg | Medicament compositions containing anticholinergically-effective compounds and betamimetics |
US20040002548A1 (en) * | 1999-05-12 | 2004-01-01 | Boehringer Ingelheim Pharma Kg | Medicament compositions containing anticholinergically-effective compounds and betamimetics |
ES2165768B1 (en) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | NEW DERIVATIVES OF QUINUCLIDINE AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM. |
US6314956B1 (en) | 1999-09-08 | 2001-11-13 | Duke University | Pulmonary delivery of NO group-containing compound in gas form to treat respiratory, cardiac and blood disorders |
US7045152B2 (en) | 1999-09-08 | 2006-05-16 | Duke University | Treating pulmonary disorders with gaseous agent causing repletion of GSNO |
TW200400821A (en) * | 1999-11-02 | 2004-01-16 | Pfizer | Pharmaceutical composition (II) useful for treating or preventing pulmonary hypertension in a patient |
WO2001051046A1 (en) * | 2000-01-14 | 2001-07-19 | University Of Virginia Patent Foundation | Airway alkalinization as therapy for airway diseases |
EA005649B1 (en) | 2000-08-11 | 2005-04-28 | Дэвид Р. Уитлок | Compositions including ammonia oxidizing bacteria to increase production of nitric oxide and nitric oxide precursors and methods of using same |
EP1333823B1 (en) * | 2000-10-16 | 2010-03-31 | Duke University | Therapeutic use of aerosolized s-nitrosoglutathione in cystic fibrosis |
US20020137764A1 (en) * | 2000-10-31 | 2002-09-26 | Karin Drechsel | Inhalable formulation of a solution containing a tiotropium salt |
BR0115016A (en) * | 2000-10-31 | 2005-05-03 | Boehringer Ingelheim Pharma | Formulation of inhalable solution with a tiotropium salt |
US20020151541A1 (en) * | 2000-10-31 | 2002-10-17 | Michel Pairet | Pharmaceutical compositions containing tiotropium salts and antihistamines and their use |
US7776315B2 (en) * | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
EP1341538B1 (en) * | 2000-10-31 | 2009-12-23 | Boehringer Ingelheim Pharma GmbH & Co.KG | Medicament compositions with salts of tiotropium and epinastin for the therapy of respiratory diseases |
DE10062712A1 (en) * | 2000-12-15 | 2002-06-20 | Boehringer Ingelheim Pharma | New drug compositions based on anticholinergics and corticosteroids |
US20100310477A1 (en) * | 2000-11-28 | 2010-12-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg. | Pharmaceutical compositions based on anticholingerics and additional active ingredients |
US6780849B2 (en) | 2000-12-21 | 2004-08-24 | Scimed Life Systems, Inc. | Lipid-based nitric oxide donors |
DE10111843A1 (en) * | 2001-03-13 | 2002-09-19 | Boehringer Ingelheim Pharma | Compounds for the treatment of inflammatory diseases |
US20030070674A1 (en) * | 2001-10-12 | 2003-04-17 | Bryan Perry | Use of aerosolized compounds in the treatment of exercise induced pulmonary hemorrhage in an equine |
GB0125222D0 (en) * | 2001-10-19 | 2001-12-12 | Barts & London Nhs Trust | Composition for the treatment of microbial infections |
WO2003057380A2 (en) * | 2002-01-11 | 2003-07-17 | Whitlock David R | Compositions including ammonia oxidizing bacteria and methods of using same |
ITMI20020148A1 (en) * | 2002-01-29 | 2003-07-29 | Nicox Sa | NEW CORTICOSTEROIDS |
WO2003086282A2 (en) * | 2002-04-05 | 2003-10-23 | Nitromed, Inc. | Nitric oxide donors, compositions and methods of use |
DE60302454T2 (en) * | 2002-04-19 | 2006-08-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | BETA AGONISTS COMPOUNDS WITH STICK OXIDE DONATOR GROUPS AND REACTIVE OXYGEN SPECIES CATEGORIES AND THEIR USE IN THE TREATMENT OF AIRWAY FLUCTUATIONS |
KR20050004155A (en) * | 2002-05-16 | 2005-01-12 | 파마시아 코포레이션 | Methods for the treatment of respiratory diseases and conditions using a selective inos inhibitor |
US20040038947A1 (en) | 2002-06-14 | 2004-02-26 | The Gov. Of The U.S. Of America As Represented By The Sec. Of The Dept. Of Health & Human Services | Method of treating ischemia/reperfusion injury with nitroxyl donors |
US6936639B2 (en) * | 2002-08-21 | 2005-08-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Nitroxyl progenitors in the treatment of heart failure |
US8133903B2 (en) * | 2003-10-21 | 2012-03-13 | Los Angeles Biomedical Research Institute at Harbor—UCLA Medical Center | Methods of use of inhibitors of phosphodiesterases and modulators of nitric oxide, reactive oxygen species, and metalloproteinases in the treatment of peyronie's disease, arteriosclerosis and other fibrotic diseases |
AU2003286555A1 (en) * | 2002-10-22 | 2004-05-13 | Harbor-Ucla Research And Education Institute | Phosphodiester inhibitors and nitric oxide modulators for treating peyronie's disease, arteriosclerosis and other fibrotic diseases |
AU2003278565A1 (en) * | 2002-10-25 | 2004-05-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments |
US7240843B2 (en) * | 2003-01-22 | 2007-07-10 | Lobar Code Technologies, Inc. | Universal club card and real-time coupon validation |
WO2004089395A2 (en) * | 2003-04-01 | 2004-10-21 | Aventis Pharmaceuticals Inc. | Use of an inhibitor of cathepsin-s or -b to treat or prevent chronic obstructive pulmonary disease |
US20050009789A1 (en) * | 2003-05-13 | 2005-01-13 | The Government Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Service | Cyclooxygenase inhibition with nitroxyl |
US20040265238A1 (en) * | 2003-06-27 | 2004-12-30 | Imtiaz Chaudry | Inhalable formulations for treating pulmonary hypertension and methods of using same |
WO2005004884A2 (en) | 2003-07-09 | 2005-01-20 | The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Use of nitrite salts for the treatment of cardiovascular conditions |
WO2005030147A2 (en) * | 2003-09-26 | 2005-04-07 | Whitlock David R | Methods of using ammonia oxidizing bacteria |
WO2005063732A1 (en) * | 2003-12-23 | 2005-07-14 | Microbia, Inc. | Compounds and methods for the treatment of asthma |
US7362274B1 (en) * | 2004-07-09 | 2008-04-22 | Huan-Cheng Lien | Coupled feed-in butterfly shaped left/right hand circularly polarized microstrip antenna |
WO2006125123A2 (en) * | 2005-05-19 | 2006-11-23 | University Of Cincinnati | Methods for treating bacterial respiratory tract infections in an individual using acidified nitrite |
WO2007002444A1 (en) * | 2005-06-23 | 2007-01-04 | Johns Hopkins University | Thiol-sensitive positive inotropes |
CN102134269A (en) * | 2005-09-02 | 2011-07-27 | 尼科克斯公司 | Nitrooxy derivatives of glucocorticoids |
GB0607402D0 (en) * | 2006-04-12 | 2006-05-24 | Barts & London Nhs Trust | Therapeutic composition and use |
US20080193385A1 (en) * | 2007-02-08 | 2008-08-14 | Todd Maibach | Compositions and methods for treating neuropathy |
EP1964550A1 (en) * | 2007-03-01 | 2008-09-03 | NicOx S.A. | Glucocorticoid-nitrooxyderivative compositions |
AU2008345034A1 (en) * | 2007-12-27 | 2009-07-09 | Aires Pharmaceuticals, Inc. | Aerosolized nitrite and nitric oxide - donating compounds and uses thereof |
US9086411B2 (en) * | 2007-12-27 | 2015-07-21 | Duke University | Resin assisted capture of cysteine-modified proteins/peptides and determination of presence and location of modification |
EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
US20110177508A1 (en) * | 2008-07-22 | 2011-07-21 | Bestor Timothy H | Universal methylation profiling methods |
JP5520948B2 (en) * | 2008-07-31 | 2014-06-11 | ニコックス エス エイ | Glucocorticoids linked to nitrates via an aromatic linker at position 21 and their use in ophthalmology |
WO2010015528A1 (en) | 2008-08-05 | 2010-02-11 | Nicox S.A. | New no-releasing steroids for the treatment of retina and macula lutea diseases |
ES2616051T3 (en) | 2008-12-02 | 2017-06-09 | Wave Life Sciences Japan, Inc. | Method for the synthesis of modified nucleic acids in the phosphorus atom |
AU2010270714B2 (en) | 2009-07-06 | 2015-08-13 | Wave Life Sciences Ltd. | Novel nucleic acid prodrugs and methods use thereof |
WO2011063339A1 (en) * | 2009-11-23 | 2011-05-26 | Cardioxyl Pharmaceuticals, Inc. | Nitroxyl donors for the treatment of pulmonary hypertension |
AU2010328234B2 (en) * | 2009-12-07 | 2016-05-12 | Cardioxyl Pharmaceuticals, Inc. | N-acyloxysulfonamide and N-hydroxy-N-acylsulfonamide derivatives |
CN105130855B (en) | 2009-12-07 | 2018-05-25 | 约翰斯霍普金斯大学 | Succinylated hydroxy amine derivatives and application thereof |
US8716268B2 (en) | 2010-06-07 | 2014-05-06 | Chao Liu | Nitrate esters of corticoid compounds useful as diuretics |
US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
EP2734208B1 (en) | 2011-07-19 | 2017-03-01 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
JP6246121B2 (en) | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | Chiral nucleic acid adjuvant |
CN107011400B (en) | 2012-07-13 | 2021-05-25 | 波涛生命科学有限公司 | Asymmetric auxiliary group |
MX2015000577A (en) | 2012-07-13 | 2015-08-14 | Wave Life Sciences Pte Ltd | Chiral control. |
US10337049B2 (en) | 2013-06-17 | 2019-07-02 | The Trustees Of Columbia University In The City Of New York | Universal methylation profiling methods |
JP6595470B2 (en) | 2013-07-31 | 2019-10-23 | ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィア | Compositions and methods for treating fatty acid metabolism disorders |
US10047042B2 (en) * | 2013-11-01 | 2018-08-14 | Glytech, Inc. | Method for producing D-form or L-form amino acid derivative having thiol group |
US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
US10149905B2 (en) | 2014-01-15 | 2018-12-11 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
KR102423317B1 (en) | 2014-01-16 | 2022-07-22 | 웨이브 라이프 사이언시스 리미티드 | Chiral design |
CA2938994A1 (en) | 2014-02-10 | 2015-08-13 | Patara Pharma, LLC | Inhalable formulations of sodium cromolyn with improved bioavailability |
DK3104854T3 (en) | 2014-02-10 | 2020-05-04 | Respivant Sciences Gmbh | MAST-CELL STABILIZERS FOR HEALTH DISEASE TREATMENT |
US20170037363A1 (en) | 2014-04-15 | 2017-02-09 | Aobiome Llc | Ammonia-oxidizing nitrosomonas eutropha strain d23 |
US11225640B2 (en) | 2014-04-15 | 2022-01-18 | Aobiome Llc | Ammonia oxidizing bacteria for treatment of psoriasis |
US10238625B2 (en) | 2015-08-07 | 2019-03-26 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
US10265296B2 (en) | 2015-08-07 | 2019-04-23 | Respivant Sciences Gmbh | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
US10590063B2 (en) | 2015-11-06 | 2020-03-17 | The Children's Hospital Of Philadelphia | Compositions and methods for the treatment of fatty acid metabolism disorders |
RU2745748C2 (en) | 2016-06-02 | 2021-03-31 | Эббви Инк. | Agonist of the glucocorticoid receptor and its immunoconjugates |
EP3506893A4 (en) | 2016-08-31 | 2020-01-22 | Respivant Sciences GmbH | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
EP3522983A4 (en) | 2016-10-07 | 2020-06-03 | Respivant Sciences GmbH | Cromolyn compositions for treatment of pulmonary fibrosis |
JP7330101B2 (en) | 2016-11-08 | 2023-08-21 | レゲネロン ファーマシューティカルス,インコーポレーテッド | Steroids and their protein conjugates |
EP3624894A1 (en) | 2017-05-18 | 2020-03-25 | Regeneron Pharmaceuticals, Inc. | Cyclodextrin protein drug conjugates |
PT3658192T (en) | 2017-12-01 | 2021-06-25 | Abbvie Inc | Glucocorticoid receptor agonist and immunoconjugates thereof |
JP2021523147A (en) | 2018-05-09 | 2021-09-02 | レゲネロン ファーマシューティカルス,インコーポレーテッド | Anti-MSR1 antibody and how to use it |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1238912B (en) * | 1964-01-31 | 1967-04-20 | Thomae Gmbh Dr K | Process for the preparation of new esters of triamcinolone-16alpha, 17alpha-acetonide |
GB1082573A (en) * | 1965-02-12 | 1967-09-06 | Boots Pure Drug Co Ltd | Improvements in the preparation of steroid esters |
FR1469675A (en) * | 1965-02-12 | 1967-02-17 | Boots Pure Drug Co Ltd | Process for the preparation of steroid esters and products obtained |
US3639434A (en) * | 1967-02-02 | 1972-02-01 | Boots Pure Drug Co Ltd | 17-acyloxysteroids and their manufacture |
DE1643036B2 (en) * | 1967-08-16 | 1976-04-15 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | NEW 11 BETA HALOGEN STEROIDS, THESE MEDICINAL PRODUCTS AND THE METHOD OF MANUFACTURING THEM |
HU164115B (en) * | 1971-05-07 | 1973-12-28 | ||
HU163145B (en) * | 1971-09-23 | 1973-06-28 | ||
DE2236115A1 (en) * | 1972-07-20 | 1974-02-07 | Schering Ag | METHOD OF PRODUCTION OF DELTA HIGH 4.9(11).16 -3.20DIKETOSTEROIDS |
US5274002A (en) * | 1987-04-14 | 1993-12-28 | Warner-Lambert Company | Trisubstituted phenyl analogs having activity for congestive heart failure |
US5570683A (en) | 1990-12-05 | 1996-11-05 | The General Hospital Corporation | Methods and devices for treating pulmonary vasoconstriction and asthma |
IL101406A (en) * | 1991-03-29 | 1998-02-08 | Brigham & Womens Hospital | Pharmaceutical compositions containing s-nitrosothiol derivatives |
DK1023900T3 (en) * | 1991-11-14 | 2005-06-06 | Brigham & Womens Hospital | Pharmaceutical composition containing S-nitroso-lipoproteins and use thereof |
AU3237193A (en) | 1991-12-11 | 1993-07-19 | Brigham And Women's Hospital | S-nitrosothiols as smooth muscle relaxants and therapeutic uses thereof |
US5728705A (en) * | 1993-10-04 | 1998-03-17 | The Trustees Of Columbia University In The City Of New York | Method of inducing vasorelaxation to treat pulmonary hypertension |
US5475003A (en) * | 1994-03-03 | 1995-12-12 | Syntex (U.S.A.) Inc. | 8-phenylcyclopentenoquinoline and 8-phenylcyclohexenoquinoline derivatives |
DE19501482A1 (en) * | 1995-01-19 | 1996-07-25 | Bayer Ag | 2,9-disubstituted purine-6-ones |
US5703073A (en) * | 1995-04-19 | 1997-12-30 | Nitromed, Inc. | Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs |
US6051588A (en) * | 1995-04-19 | 2000-04-18 | Nitromed Inc | Nitroso esters of β-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs |
US5792758A (en) * | 1995-12-08 | 1998-08-11 | G. D. Searle & Co. | Steroid nitrite ester derivatives useful as anti-inflammatory drugs |
US5707984A (en) * | 1995-12-08 | 1998-01-13 | G. D. Searle & Co. | Steroid nitrite/nitrate ester derivatives useful as anti-inflammatory drugs |
US5932538A (en) * | 1996-02-02 | 1999-08-03 | Nitromed, Inc. | Nitrosated and nitrosylated α-adrenergic receptor antagonist compounds, compositions and their uses |
US5824669A (en) * | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
US5837698A (en) | 1996-05-02 | 1998-11-17 | G. D. Searle & Co. | Steroid nitrite and nitrate ester derivatives useful as anti-inflammatory drugs |
US5985862A (en) | 1996-05-02 | 1999-11-16 | G.D. Searle & Co. | Pharmaceutical compositions having steroid nitrate ester derivatives useful as anti-inflammatory drugs |
IT1285770B1 (en) | 1996-10-04 | 1998-06-18 | Nicox Sa | CORTICOID COMPOUNDS |
US6331543B1 (en) * | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
IT1303671B1 (en) | 1998-07-28 | 2001-02-23 | Nicox Sa | SALTS OF NITRIC ACID WITH ACTIVE DRUGS IN THE TREATMENT OF DISEASES OF THE RESPIRATORY SYSTEM |
IT1311923B1 (en) | 1999-04-13 | 2002-03-20 | Nicox Sa | PHARMACEUTICAL COMPOUNDS. |
IT1314184B1 (en) | 1999-08-12 | 2002-12-06 | Nicox Sa | PHARMACEUTICAL COMPOSITIONS FOR THE THERAPY OF STRESS-OXIDATIVE CONDITIONS |
US6706724B2 (en) * | 2000-12-21 | 2004-03-16 | Nitromed, Inc. | Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use |
-
1996
- 1996-03-22 US US08/620,882 patent/US5824669A/en not_active Expired - Lifetime
-
1997
- 1997-03-19 WO PCT/US1997/004319 patent/WO1997034871A1/en active Application Filing
- 1997-03-19 EP EP97916818A patent/EP0904266A4/en not_active Withdrawn
- 1997-03-19 CA CA2248800A patent/CA2248800C/en not_active Expired - Fee Related
- 1997-03-19 JP JP9533628A patent/JP2000509016A/en not_active Ceased
- 1997-03-19 AU AU25336/97A patent/AU733202B2/en not_active Ceased
-
1998
- 1998-09-18 US US09/157,242 patent/US6197762B1/en not_active Expired - Fee Related
- 1998-12-23 US US09/219,476 patent/USRE37116E1/en not_active Expired - Lifetime
-
2000
- 2000-10-13 US US09/689,851 patent/US6579863B1/en not_active Expired - Fee Related
-
2003
- 2003-05-05 US US10/428,936 patent/US7160920B2/en not_active Expired - Fee Related
-
2006
- 2006-11-28 US US11/604,677 patent/US7345037B2/en not_active Expired - Fee Related
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009037584A2 (en) * | 2007-08-10 | 2009-03-26 | Topigen Pharmaceuticals Inc. | Combination of nitroderivatized steroid and bronchodilator for treating respiratory disease |
WO2009037584A3 (en) * | 2007-08-10 | 2011-04-28 | Nicox S.A. | Combination of nitroderivatized steroid and bronchodilator for treating respiratory disease |
WO2009071990A2 (en) * | 2007-08-31 | 2009-06-11 | Topigen Pharmaceuticals Inc. | No-donating cordicosteroid with improved pharmacokinetic, anti-inflammatory and vasodilatory properties |
WO2009071990A3 (en) * | 2007-08-31 | 2011-05-05 | Topigen Pharmaceuticals Inc. | No-donating cordicosteroid with improved pharmacokinetic, anti-inflammatory and vasodilatory properties |
Also Published As
Publication number | Publication date |
---|---|
US5824669A (en) | 1998-10-20 |
AU2533697A (en) | 1997-10-10 |
EP0904266A4 (en) | 2001-09-19 |
CA2248800C (en) | 2012-02-21 |
JP2000509016A (en) | 2000-07-18 |
AU733202B2 (en) | 2001-05-10 |
US7160920B2 (en) | 2007-01-09 |
WO1997034871A1 (en) | 1997-09-25 |
US7345037B2 (en) | 2008-03-18 |
US20030199529A1 (en) | 2003-10-23 |
US6579863B1 (en) | 2003-06-17 |
US6197762B1 (en) | 2001-03-06 |
EP0904266A1 (en) | 1999-03-31 |
USRE37116E1 (en) | 2001-03-27 |
US20070155781A1 (en) | 2007-07-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2248800A1 (en) | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders | |
DK166213C (en) | TIGOGENIN-CELLOBIOSIDE HEPTA ACETATE COMPOUNDS AND PROCEDURES FOR PREPARING IT | |
WO2004066920A2 (en) | 17-carbamoyloxy cortisol derivatives as selective glucocorticoid receptor modulators | |
SU1567124A3 (en) | Method of obtaining derivatives of beta-d-phenylthioxylozides | |
KR19990076859A (en) | 17.Beta.-Lactone Derivatives of Carboxy, Carbothio and Amide Androstane Derivatives | |
AU2003210161B2 (en) | New corticosteroids | |
US6288050B1 (en) | Steroid sulfatase inhibitors and methods for making and using the same | |
US4874773A (en) | 3-Aminocarbonyl-1,4-dihydropyridine-5-carboxylic acid compounds, and pharmaceutical composition containing the same | |
EP1946758A1 (en) | Treatment of acute myeloid leukemia | |
Paul et al. | Iron (III) acetates | |
US5116985A (en) | Isoquinoline derivatives and salts thereof | |
EP0435235B1 (en) | Isoquinoline derivatives and salts thereof as protease inhibitors. | |
DE3534765A1 (en) | Medicaments containing acylanilides, novel acylanilides, their use and process for their preparation | |
Winn | Ring opening of 3-chloro-4-nitroisothiazole with amines | |
JP2886586B2 (en) | Novel guanidinobenzoic acid derivatives and their acid addition salts | |
Drawbaugh et al. | Synthesis and biological activity of 3, 5-dinitro-4-and-2-(1H-purin-6-ylthio) benzoates, prodrugs of 6-mercaptopurine | |
EP2552913B1 (en) | Method for synthesis of tiotropium bromide | |
WO2005051903A1 (en) | Vitamin d-derived monohalogenovinyl compounds | |
Van den Heuvel et al. | Synthesis of 6β‐methyl analogues of mifepristone, new selective antiprogestagens | |
JPH02167283A (en) | Spiro compound | |
Desseaux et al. | Synthesis and properties of phosphodiester and triester derivatives of AZT with tethered potential ribonucleases | |
JPS5649360A (en) | 2-oxoquinoline derivative | |
JPS63297392A (en) | Phospholipid type imidazole compound | |
JPS58116500A (en) | Sterol derivative | |
TH14417EX (en) | Process for the preparation of substitutated steroid chol diene |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |
Effective date: 20140319 |