WO2001032621A1

WO2001032621A1 - Novel indole derivatives and drugs containing the same as the active ingredient

Info

Publication number: WO2001032621A1
Application number: PCT/JP2000/007590
Authority: WO
Inventors: Koji Nishimura; Yasuhiro Kuramoto; Koichi Tamura; Yuzo Hirao; Hirotaka Amano; Mitsuhiko Osaki; Jiro Yoshida; Shizuka Aoki; Kenji Sato
Original assignee: Wakunaga Pharmaceutical Co., Ltd.
Priority date: 1999-10-29
Filing date: 2000-10-27
Publication date: 2001-05-10
Also published as: AU7962200A

Abstract

Indole derivatives of general formula (1) or salts thereof; drugs containing the derivatives or the salts as the active ingredient; and intermediates for the preparation of the same: [wherein R1 is an amino-protecting group or COR8 (wherein R8 is aryl or the like); R2 is H, alkyl, aryl, or the like; R3 is cyano, -COR9 (wherein R9 is H, alkyl, or the like), or S(O)¿n-R?12 (wherein R12 is alkyl, aralkyl, aryl, or the like; and n is an integer of 0 to 2); and R?4, R5, R6 and R7¿ are each independently H, alkyl, alkynyl, aralkyl, alkoxy, aralkyloxy, halogeno, trifluoromethanesulfonyloxy, aryl, or the like]. The compounds (1) or salts thereof exhibit an excellent chymase activity and are useful as preventive or therapeutic drugs for circulatory diseases, inflammation, immunologic diseases, allergic diseases, eye diseases, complications of diabetes, collagen disease, and obesity.

Description

Description New indole derivatives and pharmaceuticals containing them as active ingredients

The present invention relates to a novel indole derivative having a chimase inhibitory activity or a salt thereof, a medicament containing the same as an active ingredient, and a production intermediate thereof. Background art

The renin-angiotensin system is one of the mechanisms that regulate the blood pressure of the body. Angiotensinogen is generated from angiotensinogen by renin, and is converted to angiotensin II (hereinafter referred to as “ΑΠ”) by angiotensin converting enzyme (hereinafter referred to as ACE). This All is a potent vasopressor that induces blood pressure elevation by contracting peripheral blood vessels and exciting sympathetic nerves, and is considered to be a cause of hypertension and heart failure.

In addition, All promotes gene expression of proto-oncogenes and growth factors, or directly acts on cardiomyocytes, stromal cells, vascular endothelial cells, and vascular smooth muscle cells to promote cell proliferation and hypertrophy. It is known that it promotes migration, extracellular matrix hyperplasia, and conversely, tissue remodeling (remodeling) consisting of cell injury and cell death. It has become clear that it is deeply involved in progress (Hyper tension, Vol. 13, 706-711, 1989).

Previously, it was thought that only ACE was involved in the production of Α 、, but Okunishi et al. Used isolated blood vessels from infused monkeys, and showed that the contraction when adding AI was low with an ACE inhibitor. On the other hand, the serine protease inhibitor chymosintin showed a high suppression rate (J. Hypertension, Vol. 2, 277-284, 1984), and Urata et al. In terms of enzyme activity, the rate of inhibition by ACE inhibitors is small, It was found that a serine protease inhibitor suppressed the inhibition by 80% (Cir Res., Vol. 66, 883-890, 1990). These facts suggested the existence of alternative pathways for AII production other than ACE, and this serine enzyme was found to be an enzyme called chymase belonging to serine protease (J. Biol. Chem., Vol. 265, 22348-22357). Therefore, chymase inhibitors suppress ACE-independent production of All and are expected as useful preventive and therapeutic agents for heart and cardiovascular diseases.

In addition, chymase has the effects of processing IL-1] 3, degrading IL-4, such as the metabolism of cytokines, the activity of intracellular mechanisms for mast cell degranulation, and chronic inflammatory pathology. For example, chymase plays a key role in graft-versus-host (GvH) disease, collagen disease, various types of fibrosis, various vasculitis, diabetic vasculopathy, and allergic diseases. It is expected that compounds that restrict gene expression and chymase inhibitors that control enzymatic activity could be new types of anti-inflammatory and anti-allergic agents.

Regarding such chymase inhibitors, quinazoline derivatives (W096 / 04248, WO97119441, JP-A-9131061) have been described so far. Benzoxacyclotridecine derivatives (Japanese Patent Application Laid-Open No. 10-87493, Japanese Patent Application Laid-Open No. 10-166666), and phenol ester derivatives (Japanese Patent Application Laid-Open No. 10-887567). Publications), but none of them have been applied clinically. Disclosure of the invention

An object of the present invention is to have a selective and potent inhibitory effect on human chymase, and to prevent and treat cardiovascular diseases, inflammation, immune system diseases, allergic diseases, etc., and also to protect mucous membranes and organs. An object of the present invention is to provide a novel compound useful as a drug, a drug for preventing cancer metastasis and invasion, and the like.

Under such circumstances, the present inventors have conducted intensive studies and as a result, the following general formula (1) has been obtained. Indole derivatives and their salts have excellent chymase inhibitory activity and prevent and treat cardiovascular diseases, inflammation, immune system diseases, allergic diseases, eye diseases, diabetic complications, collagen diseases or obesity Indole derivatives represented by the following general formula (2) are found to be useful as drugs, mucosal / organ protective agents, cancer metastasis / invasion preventive agents, or survival rate improving agents after organ transplantation. They have found that they are intermediates, and have completed the present invention.

That is, the present invention provides the following general formula (1)

[Wherein, R ¹ represents an amino protecting group or —C (R ⁸ (where R ⁸ represents an aryl group which may have a substituent or a heteroaryl group which may have a substituent) R ² represents a hydrogen atom, an alkyl group or an aryl group which may have a substituent, R ³ is a cyano group, _C〇R ⁹ (where R ⁹ is a hydrogen atom, An alkyl group which may have a substituent, —OR ¹ "(where R ^{1 ()} represents a hydrogen atom, an alkyl group or an aralkyl group) or _C〇R ^U (where R ¹¹ is Represents an amino group which may have a substituent or a cyclic amino group which may have a substituent)) or —S (〇) _n -R ¹² (where R ¹² is an alkyl group, aralkyl group, have also good Ariru group or a substituent substituted indicates heteroaryl group to good, n represents showed shown) an integer of 0 to 2, R ^4, R ^5, R ⁶ and R ⁷ may be the same or different and each have a hydrogen atom, an alkyl group which may have a substituent, an alkynyl group which may have a substituent, an aralkyl group, or a substituent. Alkoxy, aralkyloxy, halogen, trifluoromethanesulfonyloxy, nitro, cyano, hydroxy, carboxy, alkoxycarbonyl, aralkyloxycarbonyl, formyl, alkanoyl, A benzoyl group, an amino group which may have a substituent, an alkyl ureide group, A arylureido group, an aryl group which may have a substituent, a heteroaryl group which may have a substituent, a cycloalkanone which may have a substituent, or a group having a substituent. Cycloalkenones which may be substituted. ]

Or an indole derivative represented by the formula:

The present invention also provides a medicine containing the indole derivative or a salt thereof as an active ingredient.

The present invention also provides a chymase inhibitor comprising the indole derivative or a salt thereof as an active ingredient.

The present invention also provides a pharmaceutical composition comprising the indole derivative or a salt thereof and a pharmaceutically acceptable carrier.

The present invention also provides use of the indole derivative or a salt thereof as a medicament.

Further, the present invention provides a method for administering a compound selected from the group consisting of cardiovascular diseases, inflammation, immune system diseases, allergic diseases, eye diseases, diabetic complications, collagen diseases and obesity, which comprises administering the indole derivative or a salt thereof. And methods for treating such diseases.

Further, the present invention provides the following general formula (2)

[In the formula, R ² represents a hydrogen atom, an alkyl group or an aryl group which may have a substituent, R ³ represents a cyano group, and COR ⁹ (where R ⁹ represents a hydrogen atom and has a substituent. alkyl group which may have, -〇_R ^ID (wherein, R ^{1 ()} is a hydrogen atom, an alkyl group or § La alkyl group) or -COR ¹¹ (wherein, R ¹¹ has a substituent Represents an amino group which may be substituted or a cyclic amino group which may have a substituent)) or 1S

(〇) _n -R ¹² (where R ¹² represents an alkyl group, an aralkyl group, a substituted or unsubstituted heteroaryl group or an optionally substituted heteroaryl group, n is R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different, and have a hydrogen atom, an alkyl group which may have a substituent, or a substituent. Alkynyl group, aralkyl group, optionally substituted alkoxy group, aralkyloxy group, halogen atom, trifluoromethanesulfonyloxy group, nitro group, cyano group, hydroxy group, carboxy group , An alkoxycarbonyl group, an aralkyloxycarbonyl group, a formyl group, an alkanoyl group, a benzoyl group, an amino group which may have a substituent, an alkylureido group, and an aryl which may have a substituent Ureido group, aryl group optionally having substituent (s), heteroaryl group optionally having substituent (s), cycloalkanone optionally having substituent (s) Shows a good cycloalkenone have a substituent (provided ^{^{that, R 4, R 5, R}} 6 and R ⁷ are not simultaneously hydrogen atoms). ]

And a salt thereof. BEST MODE FOR CARRYING OUT THE INVENTION

In the general formula (1) representing the compound of the present invention, R ¹ is a hydrogen atom, an amino protecting group or one COR ⁸ (where R ⁸ is an aryl group which may have a substituent, Which represents a heteroaryl group).

Here, the term "amino protecting group" refers to an easily removable protecting group for an amino group, and examples thereof include t-tert-butoxycarbonyl, benzyloxycarponyl and the like.

_ In COR ⁸ , as the aryl group optionally having a substituent represented by R ⁸ , a monocyclic ring or a monocyclic group having 6 to 14 carbon atoms which may have 1 to 5 substituents Examples of the substituent include an alkyl group which may have a substituent (for example, Cl _-6 alkyl such as methyl, ethyl and propyl, and trifluoromethyl and the like). halogeno d_ ₆ alkyl), a halogen atom (e.g. a chlorine atom, fluorine atom, bromine atom, etc.), nitro group, hydroxy group, a carboxy group, an alkoxy force Ruponiru groups (e.g. C, _ ₆ alkoxy force Ruponiru), Ararukiru Oxycarbonyl Group (e.g., base Nji Ruo alkoxycarbonyl such Hue sulfonyl (: Bok ₄ alkyl O carboxymethyl carbonylation Le), Shiano group, an optionally substituted amino group (e.g. Amino, such as dimethyl Amino C, _ ₆ Aralkylamino, such as alkylamino, benzylamino, acetylamino, propionylamino, benzoylamino, etc., methanesulfonylamino, ethanesulfonylamino, etc., alkylsulfonylamino, benzenesulfonylamino, etc., arylsulfonylamino, etc.) (e.g. formyl, Asechiru, propionyl, Benzoiru etc.), R-S (O) n - (R is an optionally substituted alkyl group, an even better Ariru etc. have a substituent, n represents 0, 1 or 2), an alkoxy group, (for example, methoxy, ethoxy, Alkoxy, etc.), sulfonamide group (for example, sulfonamide, N-methylsulfonamide, N-ethylsulfonamide, N-propylsulfonamide, N-butylsulfonamide, N_tert-butylsulfonamide, etc.) -C w alkylsulfonamido, N _ phenylalanine sulphonamide, N _ Asechirusu C ₂ _ ₆ alkanoyloxymethyl Noi Le sulfonamides such Ruhon'amido, N _ C ₆ _ ₁₂ 7 such as N- base emission zone I le sulfonic § bromide Royle Sulfonamides), aminocarbonyl groups (eg, aminoaminocarbonyl, N-methylaminocarbonyl, N-ethylaminocarbonyl, alkylaminocarbonyl such as N, N-dimethylaminocarbonyl, benzylaminocarbonyl, etc. Aralkylaminocarbonyl), even if it has a substituent, it is a aryl group (eg, phenyl, Phenyl), a substituted or unsubstituted heteroaryl group (for example, furyl, phenyl, pyrrolyl, thiadiazolyl, pyridyl, tetrazolyl) and the like. Particularly, phenyl, 2-methylphenyl, 2-dimethyl Preferred are an aminophenyl group, a 3-dimethylaminophenyl group, a 4-dimethylaminophenyl group, a 3-dimethylamino-2-methylphenyl group, a 4-methoxyphenyl group, and a 4-chlorophenyl group.

— In COR ⁸ , as heteroaryl in the optionally substituted heteroaryl group represented by R ^s , a nitrogen atom, an oxygen atom or a sulfur atom may be 1 to 3 A 5- to 14-membered monocyclic or bicyclic heteroaryl group, such as a pyridyl group, a furyl group, a chenyl group, a pyrrolyl group, a pyrimidinyl group, an imidazolyl group, a triazolyl group, a pyrazolyl group, and an isothiazolyl group. , Isoxazolyl, thiazolyl, oxazolyl, thiadiazolyl, tetrazolyl, pyridazinyl, virazinyl, benzofuryl, benzochenyl, benzothiazolyl, benzopyranyl, quinolyl, furazinyl, naphthyridinyl And a quinazolinyl group, a cinnolinyl group, an indolyl group, an isoindolinyl group, among which a 5- to 6-membered heteroaryl group such as a pyridyl group, a furyl group, a phenyl group, a thienyl group, a thiazolyl group, an oxazolyl group and a thiaziazolyl group is preferred. New These may be substituted with 1 to 5 substituents. Examples of such a substituent include an alkyl group which may have a substituent (eg, an alkyl group such as methyl, ethyl, propyl, etc., and trifluorobenzene). halogeno such as methyl C, - ₆ alkyl, etc.), eight androgenic atom (e.g. fluorine atom, chlorine atom, bromine atom, etc.), nitro group, hydroxy group, Cal Bokishi group, an alkoxy force Ruponiru group (e.g. alkoxycarbonyl), Xia Bruno Groups, optionally substituted amino groups (eg, alkylamino such as amino, dimethylamino, etc.), alkoxy groups (eg, alkoxy such as methoxy, ethoxy, propoxy, etc.), aryl groups (eg, phenyl, naphthyl, etc.) Are mentioned.

In the general formula (1) or (2), R ² represents a hydrogen atom, an alkyl group which may have a substituent or an aryl group.

Here, examples of the alkyl in the alkyl group which may have a substituent include a linear or branched alkyl group having 1 to 8 carbon atoms. Among them, a methyl group, an ethyl group, and an n_propyl group are particularly preferable. Preferred are linear or branched alkyl groups having 1 to 5 carbon atoms, such as isopropyl, n-butyl, isobutyl, tert-butyl and n-pentyl. These may have 1 to 10 substituents. Examples of such a substituent include a halogen atom (for example, a chlorine atom and a fluorine atom), a nitro group, and a Dorokishi group, Karupokishi group, an alkoxycarbonyl group (e.g. C, _ ₆ alkoxy force Ruponiru), Shiano group, an amino group, an alkoxy group (e.g. methoxy, ethoxy, CH propoxy and the like; alkoxy), an alkylsulfonyl group Ya § Li And a sulfonyl group such as an arylsulfonyl group. Examples of the halogenoalkyl group include a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2_fluoroethyl group, a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a penfluorofluoroethyl group, 3 Furuoropuropiru group, eight Rogeno C such as heptane evening Furuoropuropiru group, - ₆ alkyl group is preferable.

Examples of the aryl group include an aromatic hydrocarbon group having 6 to 14 carbon atoms, such as a phenyl group and a naphthyl group.

In the general formula (1) or (2), R ³ is a cyano group, — COR ⁹ (where R ⁹ is a hydrogen atom or an alkyl group which may have a substituent, and R ^1D (where R ^1Q represents a hydrogen atom, an alkyl group or an aralkyl group), and one COR "(where R ¹¹ represents an amino group which may have a substituent or a cyclic amino group which may have a substituent Represents a group)) or —S (0) _N -R ¹² (wherein, R ¹² may have an alkyl group, an aralkyl group, an optionally substituted aryl group or a substituted group) Represents a heteroaryl group).

Here, — In COR ⁹ , as the alkyl group which may have a substituent represented by R ⁹ , the same as the alkyl group represented by R ² can be mentioned, but a methyl group, an ethyl group, A trifluoromethyl group, a penfluorofluoroethyl group and the like are preferred.

— In COR ⁹ , — OR ^{1 (} Examples of the alkyl group represented by in R ¹ include the same alkyl groups as those exemplified for R ⁹ , with a methyl group and an ethyl group being particularly preferred.

Among _C_〇_R ^9, - The Ararukiru group represented by R ^{1 (1} in OR ^1D, include Ararukiru the total number of carbon atoms from 6 to 14 has an alkylene chain having 1 to 6 carbon atoms, Of this Chi phenyl - Preference is given to _6- alkyl, especially benzyl, 2-phenylethyl and the like. Among _ C_〇_R ^9, as good § amino group optionally having a substituent represented by R ¹¹ in -COR ^11, other Amino groups, alkyl, (: _3-8 cycloalkyl, Ariru is 1 Examples thereof include two substituted amino groups, preferably a methylamino group, an ethylamino group, a dimethylamino group, an ethylamino group, an alkylamino group such as a tert-butylamino group, a cyclopropylamino group, a cyclobutylamino group, and a cyclobenzylamino group. And cycloalkylamino groups such as a cyclohexylamino group, an arylino group, and an arylamino group such as a naphthylamino group.

— In COR ⁹ , the cyclic amino group which may have a substituent represented by R ¹¹ in one COR is a 4- to 8-membered cyclic amino group such as an azetidinyl group, a pyrrolidinyl group, a piperidino group, a piperazino group and the like. And the substituent includes an alkyl group (eg, alkyl), a hydroxy group, an amino group, and the like.

-S (〇) _n — In R ¹² , an alkyl group, an aralkyl group, an aryl group which may have a substituent or a heteroaryl group which may have a substituent represented by R ¹² are each represented by R ² , R ^{1 ()} and R ⁸ are the same as those exemplified above, but the alkyl group is a methyl group, an ethyl group, a propyl group, etc., and the aralkyl group is a benzyl group, a phenylethyl group, etc. However, examples of the aryl group which may have a substituent include a phenyl group, a chlorophenyl group, a hydroxyphenyl group, a methylphenyl group, a methoxyphenyl group, a carboxyphenyl group, and an aminocarbonylphenyl group. As the heteroaryl group in which the group or the like may have a substituent, a pyridyl group, a benzothiazolyl group, a phenyltetrazolyl group, or the like is particularly preferable, and n is 2. If is preferred.

—S (O) _n —Preferable examples of R ¹² include a methanesulfonyl group, a phenylsulfonyl group, a benzylsulfonyl group, a pyridylsulfonyl group, a carboxyphenylsulfonyl group, and a carboxypyridinesulfonyl group.

In the general formula (1) or (2), R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different, and represent a hydrogen atom, an alkyl group which may have a substituent, or a substituent. Have Alkynyl group, aralkyl group, alkoxy group optionally having substituent (s), aralkyloxy group, halogen atom, trifluoromethanesulfonyloxy group, nitro group, cyano group, hydroxy group, carboxy group, alkoxycarbonyl group, An aralkyloxycarbonyl group, a formyl group, an alkanoyl group, a benzoyl group, an amino group which may have a substituent, an alkylureido group, an arylureido group, an aryl group which may have a substituent, A heteroaryl group which may have a substituent, a cycloalkanone which may have a substituent or a cycloalkenone which may have a substituent (in the formula (2) , R ⁴ , R ⁵ , R ⁶ and R ⁷ are not simultaneously hydrogen atoms).

Here, examples of the alkynyl in the alkynyl group which may have a substituent include ethynyl and the like, and these may be substituted with one substituent. Or an alkyl group having a substituent such as a hydroxy group or an amino group, a carboxy group, an alkoxycarbonyl group, an aryl group (eg, phenyl, naphthyl) and the like. —A methylbutyl group is preferred.

Examples of the alkoxy in the alkoxy group which may have a substituent include a straight-chain or branched-chain alkoxy group having 1 to 8 carbon atoms, among which a straight-chain or branched-chain alkoxy group having 1 to 5 carbon atoms is particularly preferable. A linear or branched alkoxy group having 1 to 5 carbon atoms such as a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a tert-butoxy group, and an n-pentyloxy group. preferable. These may be substituted with 1 to 3 substituents. Examples of such a substituent include a halogen atom (eg, a chlorine atom, a fluorine atom, a bromine atom, etc.), a nitro group, a hydroxy group, and a carboxy group. And an alkoxycarbonyl group, an aralkyloxycarbonyl group, a cyano group, an amino group and the like, and specifically, a trifluoromethoxy group, a benzyloxycarponylmethyloxy group and the like are preferable.

The aralkyloxy group includes an alkylene chain having 1 to 6 carbon atoms and a total carbon number of 6 And 14 to 14 aralkyloxy groups. Of these, a phenyl- _6- alkyloxy group is preferable, and a benzyloxy group and a 2-phenylethyloxy group are particularly preferable.

Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Among them, a bromine atom is preferable.

Examples of the alkoxycarbonyl group include an alkoxycarbonyl group having 1 to 8 carbon atoms, such as a methoxycarbonyl group, an ethoxycarbonyl group, a propoxylpropanol group, a butoxycarbonyl group, a t-tert-butoxycarbonyl group, and the like.

Examples of the aralkyloxycarbonyl group include an aralkyloxycarbonyl group having an alkylene chain having 1 to 6 carbon atoms and having a total number of 6 to 14 carbon atoms, and among them, a phenylalkyloxycarbonyl group And a benzyloxycarbonyl group, 2-phenylethyloxycarbonyl group and the like are particularly preferable.

The alkanoyl group includes an alkanoyl group having 1 to 8 carbon atoms, such as an acetyl group, a propionyl group, a butyryl group and a valeryl group.

Examples of the amino group which may have a substituent include an amino group, an alkyl group such as benzoyl, an alkylsulfonyl group (for example, methanesulfonyl, esulfonyl, propanesulfonyl, etc.), and an arylsulfonyl group. (For example, benzenesulfonyl, p-toluenesulfonyl, naphthylenesulfonyl, etc.), and an amino group substituted with an amino-protecting group, such as a tert-butoxycarbonyl group or a benzyloxycarbonyl group. Can be

Examples of the alkyl perido group include alkyl perido groups having 1 to 6 carbon atoms, such as N'-methyl ureido group, Ν'-ethyl ureido group, and N'-propyl ureido group.

Examples of the aryl perido group which may have a substituent include aryl perido groups having 6 to 14 carbon atoms, such as N'-phenyl perido group, N'-naphthyl A peridode group and an N'-alkoxycarbonylphenyl perido group. Examples of the alkyl group which may have a substituent, the aryl group which may have a substituent, and the heteroaryl group which may have a substituent include those exemplified for R ² and R ⁸ , respectively. Examples of the alkyl group which may have a substituent include a methyl group and an ethyl group, and examples of an aryl group which may have a substituent include a phenyl group and a naphthyl group. 2,4 (1H, 3H) -quinazolinedione, as a sulfamoylphenyl group, an acetylphenyl group or a methansulfonylphenyl group, may be a substituted or unsubstituted heteroaryl group. Particularly preferred are an aryl group, a pyridyl group, a pyridinium group, and an N-hydroxypyridyl group.

As good cycloalkanone be substituted, C ₄ - ₁₂ monocyclic or bicyclic alkanones, for example Shikuropen evening non, cyclohexanone and the like cyclohexane, may be substituted on the ring Examples of the group include a C alkyl group, an amino group and a carboxyl group.

As good cycloalkenone be substituted, monocyclic or bicyclic alkenone of C ₄ _ _12, for example, the cyclopentenone, cyclohexenone, tetralone, 1 _ indanone, and the like, ring Examples of the group which can be substituted above include a C alkyl group, an amino group, and a carbonyl group.

Further, depending on whether some of R ⁴ , R ⁵ , R ⁶ and R ⁷ are hydrogen atoms, the compound (1) is substituted with 0 to 4 substituents, and the compound (2) is substituted with 1 to 4 substituents. Although it can be in a form, it is preferably a mono- or di-substituted product, particularly preferably a 5-position-1-substituted product.

The salt of the compound (1) or (2) of the present invention is not particularly limited as long as it is a pharmaceutically acceptable salt. For example, (a) a salt with a mineral acid such as hydrochloric acid or sulfuric acid, (mouth) formic acid, Acetic acid, cunic acid, trichloroacetic acid, trifluoroacetic acid, salts with organic carboxylic acids such as fumaric acid, maleic acid, etc. (c) Methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, mesitylenesulfonic acid, naphthalenesulfonic acid Such as Acid addition salts such as salts with sulfonic acid, (ii) salts with alkali metals such as lithium, sodium, potassium, etc., (mouth) salts with alkaline earth metals such as calcium and magnesium, (c) ammonium Salt, (2 ') trimethylamine, triethylamine, triptylamine, pyridine, N, N-dimethylaniline, N-methylpiperidine, N_methylmorpholine, getylamine, cyclohexylamine, proforcein, dibenzylamine, N Base addition salts such as salts with nitrogen-containing organic bases such as —benzyl— / 3-phenethylamine, 1-phenamine, and N, N′-dibenzylethylenediamine.

The compound (1) or (2) of the present invention or a salt thereof can exist not only in an unsolvated form but also as a hydrate or a solvate. Accordingly, the compounds of the present invention are meant to include all crystalline forms and hydrates or solvates thereof.

The compound (1) or (2) of the present invention or a salt thereof may be a geometric isomer such as a cis-form or a trans-form, or an optical isomer such as a d-form or a one-form depending on the type and combination of the substituents. Although various isomers may exist, the present invention includes all such isomers.

The compound of the present invention can be produced by Production Methods 1 and 2 shown below.

[Production method 1]

Among the compounds of the present invention (1) or (2), R ³ is - S (〇) _[pi - a R ¹² a compound (1 - Alpha), (1 one beta), (1 - C) and (1-D ) Can be manufactured by the following steps.

[In the formula, Ri, R ² , R ⁴ , R ⁵ , R ⁶ , RR ¹² and n are the same as those described above. ]

That is, the aniline derivative (A) or the phenylhydrazine derivative (B) is used as a starting material, and is reacted with a thiocarbonyl compound (D) to be cyclized, or the indole derivative (C) is used as a starting material. The compound (1-A) of the present invention can be obtained by sulfidation.

If necessary, the compound (1-1A) is subjected to sulfide oxidation at the 3-position and N-acylation at the 1-position to give the compounds (1_B), (1-1C) and (1-D) of the present invention. ) Can be manufactured.

The cyclization reaction of the aniline derivative (A) is carried out, for example, by reacting the compound (A) with the corresponding compound. Carbonyl compound (D) and perchloric acid such as tert-butyl perchlorate, and triethylamine, diisopropylethylamine, 1,8-diazabicyclo

[5.4.0] Aromatic hydrocarbons such as benzene, toluene, xylene, etc. in the presence of organic bases such as pendene (DBU); getyl ether, tetrahydrofuran, dioxane, monoglyme Ethers such as dimethyl chloride, diglyme, etc .; halogenated hydrocarbons such as dimethylene chloride, chloroform, tetrachlorosilane, etc .; non-protons such as acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide, etc. In a solvent such as a polar solvent, -78: to 50 ° C, preferably 1 to 78 ° C to room temperature, for 10 minutes to 72 hours, preferably for 1 to 12 hours. Can be.

The cyclization reaction of the phenylhydrazine derivative (B) is carried out, for example, by reacting the compound (B) with the corresponding α-thiocarbonyl compound (D) in an alcohol solvent such as methanol, ethanol, propanol or tert-butanol at room temperature to 2 ° C. The reaction can be carried out by reacting at 0 ° (: preferably at 50 to 120 for 10 minutes to 72 hours, preferably for 1 to 12 hours. The reaction can also be carried out in the presence of an excess of a mineral acid, an organic acid such as acetic acid, or a Lewis acid such as aluminum chloride, zinc chloride or boron fluoride in an amount from a catalytic amount to an excess amount.

Surufi de of the compound (C), for example compound (C) and the corresponding disulfide compound R ^I2 SSR ¹² lithium hydroxide, sodium hydride, calcium hydride such any metal hydrides; sodium hydroxide, Inorganic salts such as potassium, sodium carbonate, carbonated lime, etc .; In the presence of bases such as sodium alkoxide such as sodium methoxide, sodium methoxide, potassium tert-butoxide, etc., benzene, toluene, xylene, etc. Aromatic hydrocarbons; ethers such as getyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme; aprotic polar solvents such as acetonitrile, N, N-dimethylformamide, dimethylsulfoxide, etc. In the solvent, The reaction can be carried out at a temperature of 50 ° C to 200 ° C (preferably at 0 ° C to 100 ° C for 10 minutes to 72 hours, preferably for 1 to 12 hours. it can.

As the sulfide oxidation, generally known ones can be used. Preferably, benzene, toluene, and the like are used in the presence of organic peroxides such as m-chloroperbenzoic acid and magnesium monoperfluoric acid and hydrogen peroxide. Aromatic hydrocarbons such as xylene; in solvents such as halogenated hydrocarbons such as methyl chloride, chloroform, carbon tetrachloride, etc .: — 30 ° C. to 100 ° C .; Preferably, the reaction can be carried out at a temperature of −10 ° C. to room temperature for 10 minutes to 72 hours, preferably 1 to 12 hours.

The N-acylation reaction is a conventional acylation reaction, for example, when the compound (1-A) is activated with an activated acid such as the corresponding acid halide, and then with a compound such as lithium hydride, sodium hydride, calcium hydride, etc. Metal hydrides; inorganic salts such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate; sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc. Bases such as sodium alkoxide or pyridin, 4-dimethylaminopyridine, picoline, N, N-dimethylaniline, N-methylmorpholine, dimethylamine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4. 0] In the presence or absence of organic bases such as pendene (DBU) Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, and carbon benzene; aromatic hydrocarbons such as benzene and toluene; ethers such as tetrahydrofuran, getyl ether, and dioxane; acetone, and methylethyl Ketones such as ketones, aprotic polar solvents such as acetonitrile, N, N-dimethylformamide, or solvents such as ethyl acetate.

0: preferably 0 to 100, for 10 minutes to 72 hours, preferably 1 to 12 hours.

The order of the oxidation reaction and the N-acylation reaction is arbitrary, and may be appropriately selected and performed. [Production method 2]

Among the compounds (1) or (2) of the present invention, the compounds (1-1E) and (1-F) wherein R ^{3 is} —COR ⁹ can be produced by the following steps.

[Wherein, R ^3a represents —COR ⁹ , and R ¹ RR ⁴ , R ⁵ , R ^6, and R ⁷ represent the same as described above. ]

That is, a compound (1-E) having —CO R ⁹ at the 3-position can be obtained by using the indole derivative (C) as a raw material and subjecting it to acylation or oxalylation. Then, the compound (1-F) can be produced. Further, a compound in which R ³ is a cyano group can be obtained by introducing —C〇R ⁹ (R ⁹ is _OR ^{1 ()} ) and then converting the compound to a cyano group by a usual method.

For example, when R ⁹ is a hydrogen atom, N, N-dimethylformamide and oxalyl chloride or phosphorus oxychloride can be dissolved in a solvent such as N, N-dimethylformamide according to the Vi 1 smier reaction. The reaction can be carried out at 100 to 100 for 1 to 24 hours.

In the case where R ⁹ is — COR ^n, that is, the introduction of one COCOR ¹¹ group, for example, (C) and an activated dicarponyl compound such as oxalyl chloride can be obtained by converting methylene chloride, chloroform form, Halogenated hydrocarbons such as carbon chloride and benzene, aromatic hydrocarbons such as benzene and toluene, ethers such as tetrahydrofuran, getyl ether and dioxane, ketones such as acetone and methyl ethyl ketone, and acetonitrile In an aprotic polar solvent or in a solvent such as ethyl acetate for 30 minutes to 100 ° (preferably at 0 ° C. to room temperature for 10 minutes to 1 hour, and then the same as the corresponding amine. Under the conditions of 10 minutes to 72 hours, preferably 1 to 12 hours It can be carried out by reacting.

When R ⁹ is other than the above, halogenated hydrocarbons such as the conditions shown in Production Method 1 or the corresponding acid anhydride and methylene chloride, carbon form, carbon tetrachloride, and carbon benzene Benzene, toluene and other aromatic hydrocarbons, tetrahydrofuran, acetyl ether, dioxane and other ethers, acetone, methyl ethyl ketone and other ketones and the like at 130 to 100 ° C. The reaction can be performed by reacting for 1 to 24 hours.

The N-acylation reaction of compound (1-E) can be carried out by the same method as that used in Production method 1.

The indole derivative (C) used as a raw material in Production Methods 1 and 2 is a known compound and can be synthesized by a known method (J, 0rg. Chem., 59, 6372-6377 (1994) Chem. Pharm. Bull., 38 (9), 2459-2462 (1990), "Chemistry of Heterocyclic Compounds", Kinya Akiba (Science & Technology Publishing Company), etc.).

In particular, any of R ^{4 to} R ⁷ is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, or an alkynyl group which may have a substituent. When a compound is obtained, it can be efficiently produced by using a cross-coupling reaction.

For example, in compound (C), R ⁵ is an aryl group which may have a substituent, a heteroaryl group which may have a substituent, or an alkynyl group which may have a substituent. Taking a compound (C ′) in a certain case as an example, it can be produced by the following reaction formula 1.

Reaction formula 1

(C) (C) Wherein X represents a halogen atom, a trifluoromethanesulfonyloxy group, R ^5a represents an aryl group which may have a substituent, a heteroaryl group which may have a substituent or Represents an alkynyl group which may have a group, M represents a hydrogen atom, a copper atom, a lithium atom, a metal halide or a group B (OR ¹³ ) ₂ (where R ¹³ represents a hydrogen atom or a lower alkyl group; R ² , R \ R ⁶ and R ⁷ are the same as described above. ]

That is, the compound (C) is cross-coupled with the compound (F) using a transition metal catalyst or the like.

Specifically, when M of the compound (F) in the above reaction formula is copper, lithium, or a metal halide, benzene, toluene, dimethyl ether, tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide, etc. It is preferable to carry out the reaction in an inert solvent in the presence of a nickel complex, a platinum complex, preferably a palladium complex. When M is — B (OR ¹³ ) ₂ (where — B (OR ¹³ ) ₂ may form a ring), benzene, toluene, getyl ether, tetrahydrofuran, In a suitable single or mixed solvent such as dioxane, acetonitrile, N, N-dimethylformamide, methanol, ethanol, propanol, dimethoxethane, water, etc., in the presence of a nickel complex, a platinum complex, preferably a palladium complex, triethylamine, Non-nucleophilic tertiary amines such as diisopropylethylamine, potassium carbonate, sodium carbonate, sodium carbonate, cesium carbonate, thallium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, thallium hydroxide, etc. The reaction is carried out under basic conditions by adding an inorganic base or an alkoxide of these alkali metals. Preferably, the Nau. When an inorganic base that is insoluble in an organic solvent is used, it must be used as an aqueous solution, and is preferably 0 to 150 in the presence of a phase transfer catalyst such as tetra-n-butylammonium bromide or crown ether. Is preferably performed at room temperature to 120 ° C.

In the above reaction formula, the halogen atom represented by X is a chlorine atom, a bromine atom And iodine atom, preferably bromine atom and iodine atom.

In the above reaction formula, Examples of the halogenated metal represented by M, For example - ZnC l group, One MgC l group, - CuC l group, one BC 1 ₂ group, - Z n B r group, - MgB r group, A CuBr group, —BBr ₂ group, and R ¹³ include a hydrogen atom and an alkyl group (methyl group, isopropyl group). When one B (OR ¹³ ) ₂ forms a ring, 1,3,2-dioxapolynan and the like can be mentioned. Examples of the palladium catalyst used in the above reaction formula include tetrakis (triphenylphosphine) palladium, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, and a divalent palladium phosphine complex.

This reaction can be carried out by activating the catalyst in the reaction mixture. For example, tris (dibenzylideneaceton) dipalladium is added to a reaction mixture to which triphenylphosphine has been added, and the resulting activated triphenylphosphine palladium complex is used. Activation of the catalyst is performed by using a divalent palladium salt such as palladium chloride, palladium bromide, or palladium acetate and trialkyl phosphine, trialkyl phosphite, triaryl phosphine, generally dialkyl zinc, alkyl zinc halide, or dialkyl. Trifluorophenylphosphine can be reacted in the presence of a reducing agent such as magnesium, an alkylmagnesium halide, a trialkylaluminum, a dialkylaluminum halide, sodium borohydride, hydrazine, arylboronic acid, and preferably dimethylethyl zinc. The introduction of R ^{4 to} R ⁷ by the coupling reaction in the production method 1 may be performed before the sulfidation at the 3-position and the N-acylation at the 1-position, as described above. As shown in 2, it may be performed after sulfidation at the 3-position and N-acylation at the 1-position.

Reaction formula 2

(G) (H) (ΐ -Β ')

[Wherein, X, R ^5a , M, R ′, R ² , R ⁴ , R ⁶ , R ⁷ and the same are as defined above. ]

The substituents of the compounds obtained in Production Methods 1 and 2 can be converted by a desired method. For example, an amino group protected with a tert-butoxycarponyl group, a benzyloxycarponyl group, a benzyl group, etc. Deprotection is performed by a known method such as decomposition and catalytic reduction, and further, substituent conversion such as alkylation and acylation is possible.

A hydroxy group protected with a benzyl group or a tert-butyldimethylsilyl group can be deprotected by a known method such as acid hydrolysis and catalytic reduction, and further, can be converted into a substituent such as alkylation or acylation. .

The cyano group is a metal azide such as sodium azide; a trialkylsilyl azide such as trimethylsilyl azide, triethylsilyl azide; By using an azide reagent such as trialkyltin azide, it can be converted to tetrazole. Further, the alkoxycarbonyl or aralkyloxycarbonyl group can be converted to a carboxy group by a known method such as acid or alkali hydrolysis and catalytic reduction. In addition, N-tert-butylsulfonamide is converted to sulfonamide in trifluoroacetic acid, hydrochloric acid, or sulfuric acid, and further can be converted to a substituent such as acylation.

The compound of the present invention thus obtained can be isolated and purified according to a conventional method. Depending on the conditions of isolation and purification, the compound of the present invention can be obtained in the form of a salt, free carboxylic acid or free amine, which can be mutually converted as required to produce the desired compound of the present invention. The compound (1) of the present invention or a salt thereof has an excellent chymase inhibitory activity as shown in the test examples described later. Therefore, a pharmaceutical containing the compound as an active ingredient is a prophylactic / therapeutic agent for cardiovascular diseases, inflammation, immune system diseases, allergic diseases, eye diseases, diabetic complications, collagen diseases or hypertrophy, etc. It is useful as a mucosal / organ protector, a cancer metastasis / invasion preventive, or a survival improver after organ transplantation.

When the compound of the present invention (1) or a salt thereof is used as a medicine, it is formulated as a composition together with a pharmaceutically acceptable carrier for parenteral administration such as injection, rectal administration, or oral administration in solid or liquid form. can do.

Forms of the compositions according to the present invention for injection include pharmaceutically acceptable sterile water, non-aqueous solutions, suspensions or emulsions. Examples of suitable non-aqueous carriers, diluents, solvents or vehicles include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic acid esters such as ethyl oleate. Such compositions may also contain adjuvants such as preserving, wetting, emulsifying, and dispersing agents. These compositions are formulated with a sterilizing agent, for example by filtration through a bacterial retention filter or in the form of a sterile solid composition which can be dissolved in sterile water or some other sterile injectable medium immediately before use. Can be sterilized. Examples of solid preparations for oral administration include capsules, tablets, pills, powders, and granules. In preparing this solid preparation, the compound of the present invention is generally mixed with at least one inert diluent, for example, sucrose, lactose, starch and the like. The formulation may also include additional substances other than inert diluents in normal formulation such as lubricants (eg, magnesium stearate, etc.). In the case of capsules, tablets and pills, a buffer may also be included. Tablets and pills can additionally be provided with an enteric coating.

Liquid preparations for oral administration include inert diluents commonly used by those skilled in the art, such as pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like, including water. Can be In addition to strong inert diluents, the composition contains a wetting agent, milk Auxiliaries such as emollients, suspending agents, sweeteners, seasonings, and flavoring agents can also be added. In the case of a preparation for rectal administration, it is preferable to contain excipients such as cocoa butter and a suppository box in addition to the compound of the present invention.

The dose of the compound (1) of the present invention or a salt thereof depends on the properties of the compound to be administered, the route of administration, the desired treatment period and other factors, but is generally about 0.1 to about 0.5% per day; OmgZkg, especially about 0.5-50 mg / kg, is preferred. If desired, the daily dose can be administered in 2 to 4 divided doses. Example

Next, the present invention will be described in detail with reference to examples.

Reference example 1 (1)

1-phenylthio-2-propanone (Compound 1)

27.5 g of thiophenol and 23.lg of acetone were dissolved in 300 ml of dichloromethane. Under ice-cooling, 50 ml of a solution of 32.3 g of diisopropylethylamine in dichloromethane was added dropwise over 40 minutes. Thereafter, the mixture was stirred at the same temperature for 16 hours. The solvent was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel; chromatographic form) to obtain 41.5 g of the above compound.

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ: 2.28 (3Η, s), 3.67 (2H, s), 7.20-7.23 (1Η, m),

7.26-7.35 (4H, m)

Reference example 1 (2) _ (10)

The following (Compound 2)-(Compound 10) were obtained in the same manner as in Reference Example 1 (1). Reference example 1 (2)

1- (4-hydroxyphenylthio) — 2-propanone (compound 2)

Properties: yellow powder

Melting point: 77.5-78.0 ° C '(ZH8 = f' Ρ 'Ζ) 01'(s' ΕΖ) 19 '9' (S ΉΟ ΙΓ Γ (s ¾) 92: ( ^s I3aD) ¾WN-H,

(L / un _o Lz-(Nye Ot —)-τ

(Ζ) TP

(ui ¾) Ά '(s ΉΖ) 89 "8' (s ¾) Π 'g' (s Ήε) 2: 9 ( ^s I3a3) HWN-H,

^: M \-

(9 (# ^^ »Ku, / 口一 ^ く ΐ

(ZH8 = f Ί 'HI) 61 ¾) 16' 9-98 "9 '(ui ΉΙ) * 9-εΖ' 9 '(s ^l HC) 8A' (s Ή2) 99 '(s Ήε): Q ( ^e I3a3) HWN-H, 呦 ^^-

(s ₀ va ₀ ^ -2- (^: your ^-ε)-τ

(S) TP # (ZHS = i 'P ΉΙ) SC8' (, = ί Ήΐ) Z 'L' (, = ί 'ί' Ρ) \ 1 Ί '(ZHS = f Ί' Hl) Z6- 9 '(s ^< HZ) Z6'2 ^< (s'H8) 18: 9 ( ^ε 13αθ) Ν-Η, m ^-

(呦 a ^ -Z-(^ Λ ((ι7 \ ~ Ζ)-T

() ΤΡ ^ (ZH8 = f 'HI) Π' I '(、 = ί' Ρ ΉΙ) 68 Ί '(、 = f' Ρ 'Ηΐ) η' L '(ΖΗ8 = ί Ί WZZ'L' ^ WZO 'f' ^ 'UZ: Q ( ⁹ P-0SKa) ¾ -Η, a 6 s τ-s -831:

^ w-i-

(ε 邈 violence, 绿 '

ζ)-ζ

(ε) ΪΡ ^ # (ΖΗ6 = Ρ'Η εζ

'(ZH6 = f' Ρ Ή2) Α9 '9' (s 'ΗΖ) ζ' (s ¾) QZ'Z-9 ( ^s IDa3) NH, S.0 / 00df / X3d U9 / 10 OAV 7.26 (2H, d, J = 8Hz)

Reference example 1 (8)

1 _Fenrylthio-1,3-dimethylbutan-2-one (Compound 8)

Properties: colorless oil

_{'H-NMR (CDC1 3)} δ: 1.18 (9H, s), 3.94 (2H, s), 7.21 (1H, t, J = 7Hz),

7.27 (2H, t, J = 7Hz), 7.38 (2H, d, J = 7Hz)

Reference example 1 (9)

1- (4-chlorophenol) — 2-propanone (compound 9)

Properties: yellow oil

'Η-thigh (CDC1 ₃ ) δ: 2.26 (3H, s), 3.64 (2H, s), 7.26 (4H, s)

Reference example 1 (1 0)

1- (4-chlorophenylthio) 1-2-butane nonone (compound 10)

Properties: colorless oil

_{'H-NMR (CDC1 3)} (5: 1.06 (3H, t, J = 8Hz), 2.61 (2H, q, J = 8Hz), 3.66 (2H, s), 7.22-7.29 (4H, m)

Reference example 2

4-Aminophenylacetic acid benzyl ester (Compound 11)

5.4 g of 4-nitrophenylacetic acid and 4.2 g of potassium carbonate were dissolved in 80 ml of dimethylformamide. After stirring at room temperature for 20 minutes, 3.4 ml of benzyl bromide was added. The mixture was further stirred at room temperature for 17 hours. Ether 2 O Oml was added, water 200 ml, 3% sodium hydrogencarbonate 20 Oml, 0.3% hydrochloric acid 100 m, and then washed with saturated saline 1 O Oml. The organic layer was concentrated after drying. Ether 1 Om1 was added to the residue, and the mixture was filtered to obtain benzyl 4-nitrophenylacetate.

Properties: pale yellow powder

_{'H-NMR (CDC1 3)} δ: 3.78 (2Η, s), 5.16 (2H, s), 7.27-7.40 (5Η, m), 7.45 (2H, d, J = 9Hz), 8.19 (2H, d, J = 9Hz)

5.5 g of iron powder was added to 20 ml of ethanol and 20 ml of water, 2 ml of 36% hydrochloric acid was added, and the mixture was stirred at 80 ° C for 20 minutes. To this were added 20 ml of a solution of 2.7 g of benzyl ester of 4-nitrophenylacetic acid in ethanol and 20 ml of tetrahydrofuran, followed by stirring for 30 minutes. Since the reaction was in progress, 0.5 ml of 36% hydrochloric acid was further added, and the mixture was stirred for 30 minutes. Filtered through Celite. Celite was washed with 100 ml of black mouth form. The filtrate was combined and the organic layer was separated. The organic layer was concentrated after drying. 2.7 g of the above compound was obtained.

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ: 3.56 (2Η, s), 3.63 (2Η, brs), 5.12 (2H, s), 6.65 (2H, d, J = 8Hz), 6.97 (2H, d, J = 8Hz), 7.28-7.37 (5H, m)

Reference example 3 (1)

4- (phenylsulfonylmethyl) aniline (compound 12)

5 ml of thiophenol and 10.6 g of p-nitrobenzyl bromide were dissolved in 50 ml of dichloromethane. Under water cooling, 6.45 g of diisopropylethylamine was added dropwise. The mixture was further stirred at room temperature for 42 hours. 1. Washed with 300 ml of 5% hydrochloric acid. After drying, it was concentrated. The residue was subjected to column chromatography (silica gel; black form). Petroleum ether was added and filtered. As a result, 11.77 g of 4- (phenylthiomethyl) nitrobenzene as pale yellow powder was obtained.

_{'H-NMR (CDC1 3)} δ: 4.14 (2Η, s), 7.20-7.32 (5Η, m), 7.38 (2H, d, J = 8.5Hz),

8.12 (2H, d, J = 8.5Hz)

4.9 g of 4- (phenylthiomethyl) nitrobenzene was dissolved in 150 ml of dichloromethane. Under ice-cooling, 8.6 g of m-chloroperbenzoic acid was added, and the mixture was stirred at the same temperature for 30 minutes and at room temperature for 30 minutes. It was washed with 3% sodium sulfite (200 ml × 1 × 3 times) and 1.5% hydrochloric acid (100 ml). The organic layer was concentrated after drying. Petroleum ether was added and filtered. 4- (phenylsulfonylmethyl) nitrobe 5.5 g of senzen was obtained.

'H - Takeshi _{R (CDC1 3) δ: 4.41} (2Η, s), 7.30 (2Η, d, J = 8.5Hz), 7.45-7.55 (2H, m), 7.62-7.70 (3H, m), 8.14 ( 2H, d, J = 8.5Hz)

15 g of iron powder was added to 30 ml of ethanol and 20 ml of water, 6 ml of 18% hydrochloric acid was added, and the mixture was stirred at 80 for 10 minutes. To this, 5.5 g of 4- (phenylsulfonylmethyl) nitrobenzene, 23 Om 1 of warm tetrahydrofuran was added, and 3 Om 1 of ethanol was further added, followed by stirring for 2 hours. Filtered through Celite. Celite was washed with 5 Om 1 of warm tetrahydrofuran. The filtrate was distilled off under reduced pressure. 10 OmI of water was added and the solid was filtered. The layers were separated with 30 mL of porcelain form and 300 mL of saturated sodium bicarbonate. The organic layer was concentrated after drying. Petroleum ether was added to the residue, and the mixture was filtered to obtain 4.07 g of the above compound.

Properties: colorless solid

Melting point: 1 7 7— 1 7 8

_{'H-NMR (CDC1 3)} δ: 3.72 (2Η, brs), 4.20 (2Η, s), 6.55 (2Η, d, J = 8.5Hz),

6.85 (2H, d, J = 8.5Hz), 7.42-7.50 (2H, m), 7.57-7.70 (3H, m)

Reference example 3 (2)

The following (Compound 13) was obtained in the same manner as in Reference Example 3 (1).

4- (Benzylsulfonylmethyl) aniline (Compound 13)

Melting point: 148—1 48.5 ° C

_{'H-NMR (CDC1 3)} δ: 3.79 (2Η, brs), 4.03 (2Η, s), 4.10 (2Η, s), 6.69 (2Η, d, J = 8Hz), 7.16 (2H, d, J = 8Hz), 7.39 (5H, brs)

Reference example 4

2- (4-aminobenzylsulfonyl) benzoic acid methyl ester (Compound 14)

3.55 g of thiosalicylic acid! 5) -Nitrobenzyl bromide (5 g) was dissolved in tetrahydrofuran (10 Om1), and diisopropylethylamine (3.87 g) was added dropwise. The mixture was further stirred at room temperature for 4 days. The solvent was concentrated. A solid formed by adding 200 ml of 0.3% hydrochloric acid was filtered. It was washed with water (5 Om 1 × 2 times), ethanol (2 Om 1 × 4 times), and hexane (20 m IX 2 times). 5.11 g of 2- (4-nitrobenzylthio) benzoic acid as a colorless powder was obtained. 2.9 g of the suspension was suspended in 60 ml of dichloromethane and 0.3 ml of dimethylformamide. 3 ml of oxalyl chloride was added dropwise thereto. The mixture was further stirred at room temperature for 20 hours. The solvent was distilled off under reduced pressure. To the residue was added methanol 60m, tetrahydrofuran 1 Om 1 was added, and the mixture was stirred at 60 for 2 hours. The solvent was distilled off under reduced pressure. 36% hydrochloric acid (5 Om1) was added thereto, and the mixture was washed with saturated sodium hydrogencarbonate (50 m) and 3% hydrochloric acid (1 Oml). After drying, the solvent was distilled off under reduced pressure. Ether was added to the residue and filtered. 2.8 g of colorless powder of 2- (4-nitrobenzylthio) benzoic acid methyl ester was obtained.

'Η-fall (CDC1 ₃ ) δ: 3.95 (3Η, s), 4.23 (2Η, s), 7.18-7.28 (2H, m),

7.41 (1H, dd, J = 2Hz, J = 9Hz), 7.57 (2H, d, J = 9Hz), 7.97 (1H, dd, J = 2Hz, J = 8Hz), 8.17 (2H, dd, J = 2Hz) , J = 8Hz)

This was dissolved in dichloromethane 6 Om1. Under water cooling, 4.4 g of MCPBA was added, and the mixture was stirred at the same temperature for 30 minutes and further at room temperature for 2 hours. It was washed with 3% sodium sulfite 100 ml × 3 times with 0.3% hydrochloric acid 10 Oml. The organic layer was concentrated after drying. Hexane was added and filtered. 2.9 g of a yellow powder was obtained.

_{'H-NMR (CDC1 3)} δ: 4.04 (3Η, s), 4.91 (2H, s), 7.43-7.52 (3Η, m),

7.65 (1Η, dd, J = 2Hz, J = 8Hz), 7.67 (1H, t, J = 7Hz), 7.73 (1H, dd, J = 2Hz, J = 7Hz),

8.1 (2H, d, J = 8Hz)

7.5 g of iron powder was added to 2 Oml of ethanol and 1 Oml of water, 2 ml of 36% hydrochloric acid was added, and the mixture was stirred at 80 for 20 minutes. 2.8 gZ of tetrahydrofuran (25 ml) was added thereto, and the mixture was stirred for 3 hours. Filtered through Celite. Celite was washed with 5 Om 1 of tetrahydrofuran. The filtrate was distilled off under reduced pressure. To the solution was added 10 mL of chloroform, and the mixture was separated with 100 ml of saturated sodium bicarbonate. Filter insoluble matter Removed. The organic layer was concentrated after drying. 2. lg of the above compound was obtained as a yellow solid. Properties: yellow solid

Melting point: 1 3 5—1 36.5

_{'H-NMR (CDC1 3)} δ: 3.69 (2H, s), 4.02 (3H, s), 4.62 (2H, s), 6.53 (2H, d, J = 8Hz), 6.99 (2H, d, J = 8Hz), 7.42 (1H, dd, J = 2Hz, J = 8Hz), 7.54-7.64 (2H, m),

7.66 (1H, d, J = 8Hz)

Example 1 (1)

5-Bromo-3- (4-hydroxyphenylthio) -2-methylindole (Compound 15)

4-Bromophenylhydrazine hydrochloride 6.78 and 1.46 g of 1- (4-hydroxyphenylthio) -2-propanone were stirred for 21 hours under heating and reflux in tert-butyl alcohol 15 Om 1. After cooling, dichloromethane 2 O Oml was added, water 20 Om was added, 3% citric acid 20 Om was added, and the mixture was washed with saturated saline 10 Oml. The organic layer was distilled off after drying. The residue was subjected to column chromatography (silica gel; dichloromethane). 4.29 g of the above compound was obtained.

Properties: pale yellow powder

Melting point: 1 6 1 _ 1 62.5 V,

'H-NMR (DMSO-de) δ: 2.47 (3Η, s), 6.66 (2Η, dd, J = 2Hz, J = 9Hz),

6.93 (2H, dd, J = 2Hz, J = 9Hz), 7.20 (1H, dd, J = 2Hz, J = 9Hz), 7.33 (1H, d, J = 9Hz),

7.45 (lH, d, J = 2Hz), 9.36 (lH, s), 11.74 (1H, s)

Example 1 (2) — (3)

The following (Compound 16) — (Compound 17) were obtained in the same manner as in Example 1 (1). Example 1 (2)

5-Bromo_2-methyl_3_ (2-pyridylthio) indole (Compound 16) Properties: light brown powder

Melting point: 243.5-244 ° C Ή-NMR (DMSO-d ₆ ) <5: 2.44 (3H, s), 6.58 (IH, d, J = 8 Hz), 7.07 (IH, dd, J = 5 Hz, J = 7 Hz), 7.24 (IH, dd, J = 2Hz, J = 8Hz), 7.40 (2H, d, J = 8Hz), 7.52 (1H, dt, J = 2Hz, J = 8Hz),

8.38 (1H, d, J-2Hz), 11.95 (lH, s)

Example 1 (3)

2- (5-Bromo_2-methylindole-3-ylthio) benzoic acid (Compound 17)

Properties: brown powder

Melting point: 237- 239 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.43 (3Η, s), 6.55 (IH, dd, J = 2Hz, J = 8Hz),

7.11-7.14 (1H, m), 7.20-7.27 (2H, m), 7.31 (IH, d, J = 2Hz), 7.35 (IH, d, J = 8Hz), 7.94 (1H, d, J = 2Hz) , 11.91 (lH, s)

Example 2

2- (5-bromo-2-methylindole-3-ylthio) benzylester benzoate (Compound 18)

5.4 g of 2- (5-bromo-2-methylindole-3-ylthio) benzoic acid and 2.4 g of potassium carbonate were dissolved in N, N-dimethylformamide 3 Om1. 2.6 g of benzyl bromide was added and stirred for 18 hours. 10 Oml of ethyl acetate was added, and the mixture was washed twice with 20 Om1 of water. The organic layer was distilled off after drying. The residue was subjected to column chromatography (silica gel; dichloromethane). Hexane was added and the mixture was filtered to obtain 4.9 g of the above compound.

Properties: colorless powder

Melting point: 171.5-17.33.5

'H-NMR (DMS0-d ₆ ) δ 2.44 (3Η, s), 5.42 (2Η, s), 6.59 (IH, d, J = 8Hz),

7.18 (IH, t, J = 7Hz), 7.25 (1H, dd, J = 2Hz, J = 8Hz), 7.29-7.32 (2H, m),

7.38-7.46 (5H, m), 7.55 (2H, d, J = 8Hz), 7.99 (IH, dd, J = 2Hz, J = 8Hz), 11.95 (IH, s) Example 3 (1) 5-Bromo_2-methyl_3- (4-chlorophenylthio) indole (Compound 19)

3.4 g of 4-bromoaniline was dissolved in 80 ml of dichloromethane. At 50 ° C, 1 Oml of a dichloromethane solution of 2.1 g of perchloric acid t-tert-butyl ester was added dropwise over 20 minutes. The mixture was stirred at the same temperature for 20 minutes. To this was added 1 Om 1 of a solution of 4.0 g of 4- (propane phenylthio) -2-propanone in 10 minutes and stirred for 1 hour. 5 ml of a dichloromethane solution of 2.1 g of triethylamine was added, and the mixture was stirred at room temperature for 2 hours. The organic layer was separated by adding 5 Oml of water, dried and concentrated. The residue was subjected to column chromatography (silica gel; chromate form). Hexane was added and the mixture was filtered to obtain 0.91 g of the above compound.

Properties: light brown powder

Melting point: 138- 139 O

_{'H-NMR (CDC1 3)} δ: 2.49 (3Η, s), 6.92 (2Η, d, J = 9Hz), 7.12 (2H, d, J = 9Hz),

7.18-7.32 (2H, m), 7.63 (1H, s), 8.28 (1H, brs)

Example 3 (2)-(23)

The following (Compound 20)-(Compound 41) were obtained in the same manner as in Example 3 (1). Example 3 (2)

5-bromo-2-methyl-3- (4-methylphenylthio) indole (compound

20)

Properties: light brown powder

Melting point: 143-145 ° C

_{'H-NMR (CDC1 3)} δ: 2.24 (3Η, s), 2.49 (3Η, s), 6.92 (2Η, d, J = 8Hz),

6.96 (2H, d, J = 8Hz), 7.18 (1H, d, J = 8Hz), 7.24 (1H, d, J = 8Hz), 7.66 (1H, s),

8.21 (1H, brs)

Example 3 (3)

3- (benzylthio) _5-promo 2-methylindole (Compound 21) Properties: light brown powder

Melting point: 1 2 1—1 22.5. C

_{'H-NMR (CDC1 3)} δ: 1.96 (3Η, s), 3.72 (2H, s), 6.92 (2H, d, J = 9Hz),

7.11-7.28 (5H, m), 7.71 (IH, s), 7.97 (IH, brs)

Example 3 (4)

5 _Bromo-2-methyl-3 _ (3-methoxyphenylthio) indole (Compound 22)

Properties: light brown powder

Melting point: 1 2 7— 1 2 9 ° C

_{'H-NMR (CDC1 3)} δ: 2.50 (3Η, s), 3.68 (3H, s), 6.53-6.64 (3H, m),

7.09 (1H, t, J = 9Hz), 7.21 (IH, d, J = 9Hz), 7.27 (1H, d, J = 9Hz), 7.68 (IH, s), 8.29 (lH, brs)

Example 3 (5)

(2-Methyl-3-phenylthioindole-5-yl) Ethyl acetate (Compound 23)

Properties: colorless powder

Melting point: 9 0—9 0.5

Ή- thigh _{(CDC1 3) δ: 1.19 (} 3Η, t, J = 8Hz), 2.50 (3Η, s), 3.66 (2H, s),

4.11 (2H, q, J = 8Hz), 7.02-7.05 (3H, m), 7.12-7.17 (3H, m), 7.28 (IH, d, J = 8Hz), 7.43 (lH, s), 8.27 (lH , brs)

Example 3 (6)

5-Promote 2 _t e rt—butyl— 3- (phenylthio) indole (Compound 24)

Properties: brown powder

Melting point: 1 40 -1 42 ° C

_{'H-NMR (CDC1 3)} δ: 1.51 (9Η, s), 6.96 (2Η, dd, J = 2Hz, J = 8Hz), 7.03 (IH, t, J = 8Hz), 7.15 (2H, t, J = 8Hz), 7.23-7.28 (2H, m), 7.62 (IH, s), 8.35 (IH, brs) Example 3 (7)

3- (4-chlorophenyl) -2,5-dimethylindole (Compound 25) Properties: brown powder

Melting point: 141- 142 ° C

_{'H-NMR (CDC1 3)} δ: 2.40 (3Η, s), 2.48 (3Η, s), 6.94 (2Η, dd, J = 2Hz, J = 9Hz), 7.02 (IH, d, J = 9Hz), 7.10 (2H, dd, J = 2Hz, J = 9Hz), 7.26 (IH, d, J = 9Hz),

7.29 (lH, s), 8.17 (lH, brs)

Example 3 (8)

5-Acetyl-2-methyl-3-phenylthioindole (Compound 26) Properties: yellow powder

Melting point: 1 16— 1 18

_{'H-NMR (CDC1 3)} 6: 2.54 (3H, s), 2.61 (3H, s), 7.01-7.21 (5H, m),

7.38 (IH, d, J = 9 Hz), 7.89 (IH, dd, J = 2 Hz, J = 8 Hz), 8.17 (IH, s), 8.79 (IH, brs) Example 3 (9)

2-Methyl-3-phenylthioindole-5-carboxylate (27)

Properties: brown powder

Melting point: 180—180.5T:

_{'H-NMR (CDC1 3)} δ: 1.38 (3H, t, J = 7Hz), 2.53 (3Η, s), 4.36 (2Η, q, J = 7Hz), 7.01-7.05 (3H, m), 7.15 ( 2H, t, J = 8Hz), 7.35 (IH, d, J = 9Hz),

7.92 (1H, dd, J = 2Hz, J = 9Hz), 8.30 (IH, s), 8.49 (IH, brs)

Example 3 (10)

5-Promote 2-Methyl-3_phenylthioindole (Compound 28)

Properties: brown powder

Melting point: 162-164 ° C 'Η-wake R (CDC1 ₃ ) δ: 2.53 (3Η, s), 7.02 (2Η, d, J = 8Hz), 7.08 (IH, dt, J = lHz, J = 8Hz), 7.11-7.32 (4H, m), 7.69 (IH, s), 8.28 (lH, brs)

Example 3 (1 1)

5-cyano-2-methyl-3-phenylthioindole (Compound 29)

Properties: pale red powder

Melting point: 156-157 ° C

_{'H-NMR (CDC1 3)} δ: 2.56 (3Η, s), 7.01 (2H, dd, J = 2Hz, J = 8Hz),

7.08 (lH, dt, J = 2Hz, J = 8Hz), 7.17 (2H, dt, J = 2Hz, J = 8Hz),

7.42 (2H, dq, J = 2Hz, J = 8Hz), 7.87 (IH, s), 8.62 (IH, brs)

Example 3 (12)

5 _Bromo-3-.. (4-chlorophenylthio) -2-ethylindole (Compound 30)

Properties: brown oil

_{'H-NMR (CDC1 3)} 6: 1.27 (3H, t, J = 8Hz), 2.91 (2H, q, J = 8Hz),

6.92 (2H, dd, J = 2Hz, J = 7Hz), 7.12 (2H, dd, J = 2Hz, J = 7Hz), 7.22-7.32 (2H, m), 7.64 (1H, d, J = 2Hz), 8.33 (lH, brs)

Example 3 (13)

2,5-dimethyl-3-phenylthioindole (Compound 31)

Properties: brown powder

Melting point: 157—159

_{'H-NMR (CDC1 3)} δ: 2.39 (3Η, s), 2.50 (3H, s), 6.96-7.05 (3Η, m),

7.11-7.19 (2Η, m), 7.20-7.27 (2Η, m), 7.33 (IH, s), 8.15 (1H, brs)

Example 3 (14)

-Methyl-3-phenylthio-5-trifluoromethylindole (Compound 32)

Properties: colorless powder Melting point: 105.5-106 ° C

_{'H-NMR (CDC1 3)} δ 2.55 (3H, s), 7.01-7.10 (3H, m), 7.17 (2H, t, J = 8Hz),

7.43 (2H, d, J = 8Hz), 7.85 (1H, s), 8.41 (IH, brs)

Example 3 (15)

5-Benzoyl 2-methyl-3-phenylthioindole (Compound 33) Properties: Light brown powder

Melting point: 217.5-218 ° C

¾-NMR (DMS0-d ₆ ) δ: 2.51 (3 H, s), 6.98 (2Η, dd, J = 2 Hz, J = 8 Hz),

7.10 (1H, t, J = 8Hz), 7.22 (2H, t, J = 8Hz), 7.48 (2H, t, J = 8Hz),

7.55 (1H, d, J = 8Hz), 7.61 (4H, dd, J = 2Hz, J = 8Hz), 7.72 (IH, d, J = 2Hz)

Example 3 (16)

(2-Methyl-3-phenylthioindole-5-yl) Benzyl acetate (Compound 34)

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ: 2.49 (3Η, s), 3.73 (2Η, s), 5.10 (2H, s), 7.00-7.05 (3H, m), 7.05-7.10 (3H, m), 7.25 -7.35 (6H, m), 7.45 (IH, s), 8.29 (IH, brs)

Example 3 (17)

2-Methyl-5-phenylsulfonylmethyl-3-phenylthioindole (Compound 35)

Properties: brown oil

_{'H-NMR (CDC1 3)} δ: 2.50 (3Η, s), 4.37 (2Η, s), 6.90-7.18 (7H, m), 7.37-7.70 (6H, m), 8.35 (lH, brs)

Example 3 (18)

5-cyanomethyl-2-methyl-3-phenylthioindole (Compound 36) Properties: brown oil

_{'H-NMR (CDC1 3)} 6: 2.52 (3H, s), 3.78 (2H, s), 6.98-7.08 (3H, m), 7.12-7.19 (3H, m), 7.33 (IH, d, J = 9Hz), 7.44 (IH, s), 8.39 (1H, brs)

Example 3 (19)

2-Methyl-3-phenylthioindole-5-Benzyl rubonic acid ester (Compound 37)

Properties: pale red powder

Melting point: 202.5-203 ° C

_{Ή-NMR (CDC1 3) δ} 2.54 (3Η, s), 5.35 (2Η, s), 6.97-7.08 (3H, m), 7.12-7.18 (2H, m), 7.30-7.45 (6H, m), 7.94 (1H, dd, J = 2Hz, J = 9Hz), 8.34 (1H, s), 8 · 41 (IH, brs) Example 3 (20)

5-benzylsulfonylmethyl-2-methyl-3-phenylthioindole (compound 38)

Properties: yellow solid

Melting point: 78-80

_{'H-NMR (CDC1 3)} δ: 2.55 (3H, s), 3.99 (2H, s), 4.16 (2H, s), 7.01-7.04 (3H, m), 7.14-7.17 (2H, m), 7.23 -7.40 (8H, m), 8.40 (1H, brs)

Example 3 (21)

2- (2-methyl-3-phenylthioindole-5-ylmethylsulfonyl) benzoic acid methyl ester (Compound 39)

Properties: yellow solid

Melting point: 189— 189.5 ° C

_{'H-NMR (CDC1 3)} δ: 2.47 (3Η, s), 3.99 (3Η, s), 4.79 (2Η, s), 6.92 (2Η, d, J = 8Hz), 7.06 (IH, dd, J = 2Hz, J = 8Hz), 7.12-7.19 (4H, m), 7.22-7.29 (2H, m),

7.43 (2H, d, J = 8Hz), 7.58 (1H, dd, J = 2Hz, J = 8Hz), 8.31 (1H, brs)

Example 3 (22)

2-Methyl-5-Nitro-3-phenylthioindole (Compound 40)

Properties: yellow powder Melting point: 2 1 7—2 19 ° C

_{'H-NMR (CDC1 3)} δ 2.57 (3H, s), 7.02 (2H, d, J = 7Hz), 7.08 (IH, d, J = 7Hz), 7.15-7.19 (2H, m), 7.38 (IH , d, J = 8Hz), 8.10 (1H, d, J = 8Hz), 8.48 (IH, s), 8.57 (lH, brs)

Example 3 (23)

5-Promo 2-Methyl-3-methylthioindole (Compound 41)

Properties: brown solid

Melting point: 80—80.5 ° C

_{'Η - NMR (CDC1 3)} δ: 2.24 (3H, s), 2.52 (3H, s), 7.14 (1H, d, J = 8Hz),

7.24 (IH, dd, J = 2Hz, J = 8Hz), 7.81 (1H, d, J = 2Hz), 8.05 (IH, brs)

Example 4

5-amino-2-methyl-3-phenylthioindole (compound 42)

8 g of iron powder was added to 25 ml of ethanol and 25 ml of water. 3 ml of 36% hydrochloric acid was added, and the mixture was stirred at 80 for 20 minutes. To this was added a solution of 3.3 g of 2-methyl-5-nitro-3-phenylthioindole in 25 ml of ethanol and 25 ml of tetrahydrofuran, and the mixture was stirred at the same temperature for 30 minutes. The iron powder was removed by filtration with celite and washed with ethanol and tetrahydrofuran. The filtrate was distilled off under reduced pressure. The residue was extracted with dichloromethane (200 ml) and washed with saturated aqueous sodium hydrogen carbonate (200 ml). The insolubles generated at this time were removed by filtration through Celite. The organic layer was concentrated after drying. Hexane was added and the mixture was filtered to obtain 2.5 g of the above compound.

Properties: light brown powder

Melting point: 1 86— 187.5:

'H-NMR (DMS0-d ₆ ) 6 2.36 (3H, s), 4.54 (2H, brs), 6.46 (IH, dd, J = 2 Hz, J = 9 Hz), 6.51 (IH, s), 6.94 (2H , d, J = 7Hz), 7.02-7.07 (2H, m), 7.16-7.19 (2H, m),

11.14 (1H, s)

Example 5 2-methyl-5-nitroindole (compound 43)

284 mg of 2-methyl-5-twotro-3-phenylthioindole and 308 mg of thiosalicylic acid were added to 7 ml of trifluoroacetic acid, followed by stirring at 80 for 20 minutes. Distilled off under reduced pressure. 30 ml of ethyl acetate was added, and the mixture was washed with 4% sodium hydroxide 60 ml × 3 times. The organic layer was concentrated after drying. The residue was subjected to column chromatography (silica gel; black form). Hexane and ether were added and the mixture was filtered to obtain 9 Omg of the above compound.

Properties: yellow powder

Melting point: 173— 173.5

'H-NMR (DMSO-d ₆ ) δ: 2.43 (3Η, s), 6.42 (1H, s), 7.43 (1H, d, J = 9 Hz),

7.91 (1H, dd, J = 2Hz, J = 9Hz), 8.41 (1H, d, J = 2Hz), 11.69 (1H, s)

Example 6

5-Amino_2-methylindole (Compound 44)

3 g of iron powder was added to 1 Oml of ethanol and 1 Oml of water. 36% hydrochloric acid (lm1) was added, and the mixture was stirred at 8 Ot for 20 minutes. To this was added a solution of 0.8 g of 2-methyl-5-nitroindole in 6 ml of tetrahydrofuran and 3 ml of ethanol, and the mixture was further stirred for 1 hour. Filtered through Celite. Washing was performed with 3 Om 1 × 2 times each of tetrahydrofuran, ethanol, and dichloromethane. The organic layer was concentrated under reduced pressure. 5 Oml of saturated sodium hydrogen carbonate was added, and the mixture was extracted with 5 Oml of dichloromethane. After drying, it was distilled off. The residue was subjected to column chromatography (silica gel; dichloromethane) to obtain 67 Omg of the above compound.

Properties: light brown powder

Melting point: 134- 135.5 ° C

'H-NMR (DMSO-d ₆ ) δ: 2.29 (3Η, s), 4.32 (2Η, brs), 5.81 (1Η, s),

6.36 (1H, dd, J = 2Hz, J = 8Hz), 6.55 (1H, d, J = 2Hz), 6.93 (1H, d, J = 8Hz), 10.34 (1H, s) 5-tert-Butoxycarbonylamino-2-methyl-3- (2-pyridylthio) indole (Compound 45)

5-Amino-2-methylindole 6 O Omg was dissolved in tetrahydrofuran 2 Oml. Di-tert-butyl dicarbonate (88 Omg) was added, and the mixture was stirred at room temperature for 1.5 hours. The solvent was distilled off, and the residue was subjected to column chromatography (silica gel; dichloromethane). Hexane was added and filtered. 86 Omg of a colorless powder of 5_tert-butoxycarbonylamino-2-methylindole was obtained.

0.34 g of sodium hydride is suspended in 3 ml of N, N-dimethylformamide, and 0.8 g of 5-tert-butoxycarbonylamino-2-methylindole is added thereto under ice-cooling. For a minute. To this, 0.88 g of 2,2,1-dipyridyl disulfide was added, and the mixture was stirred at room temperature for 18 hours. Ethyl acetate (60 ml) was added, and the mixture was washed 4 times with 3% sodium carbonate (20 ml). After drying, it was distilled off. Hexane was added and the mixture was filtered to obtain 61 Omg of the above compound.

Properties: pale yellow powder

Melting point: 197-198

'H-NMR (DMSO-d ₆ ) δ: 1.42 (9Η, s), 2.40 (3Η, s), 6.51 (IH, d, J = 8Hz),

7.04 (1H, dd, J = 2Hz, J = 8Hz), 7.11-7.15 (IH, m), 7.16 (1H, d, J = 8Hz),

7.48 (1H, dd, J-2Hz, J = 8Hz), 7.56 (1H, brs), 8.37 (IH, d, J = 4Hz), 9.08 (IH, brs), 11.56 (1H, s)

Example 8

2-(Ν '-(2-Methyl-3-phenylthioindole-5 ml) perido) Methyl benzoate (Compound 46)

A mixture of 50 Omg of 5-amino-2-methyl-3-phenylthioindole, 36 Omg of methyl 2-isocyanatobenzoate, and 2 Omg of 4-dimethylaminopyridine was stirred at 50 ° C for 4 hours. The solvent was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel; dichloromethane) to obtain 78 Omg of the above compound. Properties: colorless powder

Melting point: 94-95.5 ° C

_{'H-NMR (CDC1 3)} δ: 2.49 (3Η, s), 3.76 (3Η, s), 6.50 (1Η, s), 6.95-7.07 (4H, m), 7.11 (2H, d, J = 7Hz) , 7.30 (2H, s), 7.42-7.53 (2H, m), 7.95 (1H, d, J = 7Hz),

8.39 (1H, s), 8.5 (1H, d, J = 8Hz), 10.36 (1H, s)

Example 9

3-(2-Methyl-3-phenylthioindole-5-yl) —2,4 (1H, 3H) -quinazolinedione (compound 47)

2- (Ν '-(2-Methyl_3-phenylthioindole-5-yl) perylene) 1 g of benzoic acid methyl ester was dissolved in 15 ml of toluene and 5 ml of dimethyl sulfoxide. 0.5 ml of 1,8_diazabicyclo [5.4.0] indene (DBU) was added, and the mixture was stirred at 110 ° C for 3 hours. The solvent was distilled off under reduced pressure. To the residue was added 30% of 3% citrate and extracted with 20% of ethyl acetate. After drying, the organic layer was distilled off under reduced pressure. Hexane was added to the residue, followed by filtration to obtain 0.91 g of the above compound.

Properties: light brown powder

Melting point: 254—256T:

'H-NMR (DMSO-d ₆ ) δ: 2.54 (3Η, s), 6.98 (2Η, d, J = 9 Hz), 7.01 (1H, d, J = 2 Hz), 7.06 (1H, t, J = 8 Hz) ), 7.18-7.21 (4H, m), 7.25 (1H, s), 7.46 (1H, d, J = 9Hz),

7.67 (1H, t, J = 8Hz), 7.90 (1H, d, J = 7Hz), 11.43 (1H, s), 11.83 (1H, s)

Example 10 (1)

5-Acetylamino-3-phenylthioindole (Compound 48)

.5-Aminoindole 4 O Omg was dissolved in tetrahydrofuran 10 ml, acetylimidazole 33 Omg and 4-dimethylaminopyridine 1 Omg were added, and the mixture was stirred at room temperature for 18 hours and further at 60 ° C for 4 hours. The solvent was distilled off under reduced pressure. Dichloromethane 3 Om1 was added to the residue, and the mixture was washed with 3% citric acid. After drying, it was concentrated. Ether was added and filtered. 0.27 g of light brown powder of 5-acetylaminoindole was obtained.

'H-NMR (DMSO-d ₆ ) δ: 2.02 (3Η, s), 6.35 (IH, s), 7.17 (1H, dd, J = 2Hz, J = 9Hz), 7.29 (2H, dd, J = 2Hz) , J = 6Hz), 7.84 (1H, s), 9.70 (IH, s), 10.96 (1H, brs)

24 Omg of sodium hydride was suspended in 1 Nm of N, N-dimethylformamide, and 348 mg of 5-acetylaminoindole was added thereto under ice cooling, followed by stirring for 30 minutes. To this was added 0.5 g of diphenyldisulfide, and the mixture was stirred at room temperature for 4 hours. 50 ml of water were added under cooling. Extracted with ethyl acetate 3 Oml. The organic layer was further washed with 3% sodium carbonate at 10 Oml × 3 times. After drying, it was concentrated. The residue was subjected to column chromatography (silica gel; chloroform-form ethyl acetate = 10Z1) to obtain 53 Omg of the above compound.

Properties: purple powder

Melting point: 8 1— 82

_{'H-NMR (CDC1 3)} 6: 2.14 (3H, s), 7.04-7.14 (3H, m), 7.16-7.18 (3H, m),

7.39 (IH, d, J = 9Hz), 7.43 (1H, s), 7.48 (IH, d, J = 2Hz), 7.62 (IH, dd, J = 2Hz, J = 9Hz),

8.46 (lH, brs)

Example 10 (2) — (6)

The following (Compound 49)-(Compound 53) were obtained in the same manner as in Example 10 (1).

Example 10 (2)

5-benzoylamino-3-phenylthioindole (Compound 49)

Properties: brown powder

Melting point: 208—209 ° C

'H-NMR (DMSO-d ₆ ) δ: 7.01 (2H, d, J = 8 Hz), 7.05 (IH, t, J = 8 Hz), 7.20 (2H, t, J = 8 Hz), 7.43-7.62 (5H , m), 7.75 (1H, d, J = 3Hz), 7.79-8.00 (3H, m), 10.15 (IH, s), 11 · 68 (1H, s) Example 10 (3) 3-phenylthio-5- (4-toluenesulfonylamino) indole (compound 50)

Properties: light brown powder

Melting point: 205 _ 206.5 ° C

'H-NMR (DMS0-d 6) 6: 2.28 (3H, s), 6.94 (2H, d, J = 7Hz), 6.96 (IH, d, J = 2Hz), 7.11 (2H, dd, J = 2Hz , J = 9Hz), 7.15-7.2 (4H, m), 7.36 (1H, d, J = 8Hz),

7.46 (2H, d, 8Hz), 7.72 (IH, d, J = 2Hz), 9 · 81 (IH, s), 11 · 65 (1H, s)

Example 10 (4)

N— (3-phenylthioindole-5-yl) — N, —phenylpereyl (Compound 51)

Properties: brown powder

Melting point: 208 _ 210

'H-NMR (DMSO-d ₆ ) δ: 6.92 (IH, t, J = 8 Hz), 7.01 (2H, d, J = 8 Hz),

7.05 (IH, t, J = 8Hz), 7.15-7.30 (5H, m), 7.35-7.45 (3H, m), 7.61 (IH, s),

7.71 (IH, d, J = 3Hz), 8.47 (1H, s), 8.53 (1H, s), 11.58 (1H, s)

Example 10 (5)

5-tert-butoxycarbonylamino-3-phenylthioindole (Compound 52)

Properties: yellow solid

Melting point: 78.5-80

'H-NMR (DMS0-d ₆ ) δ: 1.43 (9Η, s), 6.98 (2Η, d, J = 8 Hz), 6.99-7.07 (IH, m), 7.18-7.21 (3H, m), 7.36 ( (IH, d, J = 9Hz), 7.66-7.72 (2H, m), 9.14 (1H, brs), 11.57 (lH.s)

Example 10 (6)

3— (3—Fenrthio Indone 1—5—yl) 1 2, 4 (1 H, 3H) —Quina

(Compound 53) Properties: pale red powder

Melting point: 258 _ 258.5 ° C

'H-NMR (DMSO-d ₆ ) δ: 7.05-7.11 (3Η, m), 7.19-7.26 (4Η, m), 7.36 (IH, s), 7.45 (1H, t, J = 8Hz), 7.58 ( (IH, d, J = 9Hz), 7.66-7.71 (IH, m), 7.88-7.97 (2H, m), 11.47 (lH, brs), 11.89 (lH.s)

Example 1 1 (1)

5-Bromo-3-phenylthioindole (Compound 54)

1.53 g of sodium hydride was suspended in 7 Om1 of dimethylformamide, and 5 g of 5-bromoindole was added thereto under ice-cooling, followed by 6.12 g of diphenyldisulfide. The mixture was stirred at room temperature for 1 day. Water was added to the reaction solution, extracted with getyl ether, dried over anhydrous magnesium sulfate and concentrated. The residue was triturated with hexane to obtain 6.06 g of the above compound.

Properties: colorless powder

Melting point: 128-130

_{'H-NMR (CDC1 3)} δ: 7.03-7.12 (3Η, m), 7.12-7.21 (2H, m), 7.29-7.38 (2Η, m),

7.50 (IH, d, J = 3Hz), 7.75 (1H, s), 8.44 (IH, brs)

Example 1 1 (2) _ (10)

The following (Compound 55) — (Compound 63) was obtained in the same manner as in Example 11 (1).

Example 1 1 (2)

5_Bromo_3- (2-pyridylthio) indole (Compound 55)

Properties: colorless powder

Melting point: 253-255 ° C

'H-NMR (DMS0-d ₆ ) 6 6.05 (IH, d, J = 8Hz), 7.04-7.09 (IH, m),

7.33 (IH, dd, J = 8Hz, J = 2Hz), 7.50-7.58 (3H, m), 7.87 (IH, s), 8.37 (IH, d, J = 4Hz) Example 1 1 (3) 5-Promote 3 _ (4-chlorophenol) Indole (Compound 56) Properties: colorless powder

Melting point: 146-148

_{'H-NMR (CDC1 3)} δ: 6.99 (2Η, d, J = 9Hz), 7.14 (2H, d, J = 9Hz), 7.32 (IH, d, J = 9Hz),

7.36 (1H, dd, J = 9Hz, J = 2Hz), 7.50 (1H, d, J = 2Hz), 7.71 (IH, s), 8.46 (IH, brs) Example 1 1 (4)

5-Bromo-3- (4-methylphenylthio) indole (Compound 57) Properties: Brown powder

Melting point: 126 _ 128 ° C

_{'H-NMR (CDC1 3)} δ: 2.26 (3Η, s), 7.88 (IH, s), 8.09 (IH, dd, J = 7Hz, J = 2Hz),

8.22 (IH, d, J = 9 Hz), 8.51 (IH, d, J = 2 Hz), 8.81 (IH, d, J = 2 Hz), 10.06 (IH, s) Example 1 1 (5)

5-Bromo_3- (4-ditrophenylthio) indole (Compound 58) Properties: yellow powder

Melting point: 184_ 18

• H-NMR (DMS0-d 6) δ: 7.29 (1H, d, J = 9Hz), 7.41 (IH, d, J = 9Hz), 7.59 (IH, s), 7.91 (2H, d, J = 9Hz ), 7.96 (IH, s), 8.24 (2H, d, J = 9Hz), 11.91 (IH, brs)

Example 1 1 (6)

2- (5_bromoindole-3-ylthio) benzothiazole (Compound 59) Properties: yellow powder

Melting point: 222_224

'H-NMR (DMS0-d ₆ ) δ 7.28 (IH, t, J = 8 Hz), 7.38 (IH, dd, J = 9 Hz, J = 2 Hz),

7.42 (IH, t, J = 8 Hz), 7.55 (IH, d, J = 9 Hz), 7.68 (IH, d, J = 2 Hz), 7.83 (2H, d, J = 8 Hz), 8.12 (lH, d, J = 3Hz), 12.24 (lH, brs)

Example 1 1 (7)

5-(5-bromoindole-3-ylthio) 1-phenylphenyltetrazole Compound 60)

Properties: colorless powder

Melting point: 208—210 ° C

_{'H-NMR (CDC1 3)} δ: 7.33 (IH, dd, J = 9Hz, J = 2Hz), 7.47 (IH, d, J-9Hz),

7.62 (IH, d, J = 2Hz), 7.63-7.71 (3H, m), 7.71-7.80 (2H, m), 7.85 (1H, s),

12.00 (lH, brs)

Example 1 1 (8)

5-Benzyloxy-3 _ (4 _ methylphenylthio) indole (Compound 61)

Properties: brown powder

Melting point: 1 16— 1 18

_{'H-NMR (CDC1 3)} δ: 2.26 (3Η, s), 5.03 (2Η, s), 6.93-7.02 (5Η, m),

7.15 (IH, d, J = 2Hz), 7.28-7.39 (4H, m), 7.39-7.44 (3H, m), 8.31 (IH, brs) Example 11 (9)

5-benzyloxy-3-phenylthioindole (Compound 62)

Properties: light brown powder

Melting point: 1 35— 1 37 ° C

_{'H-NMR (CDC1 3)} δ: 5.03 (2Η, s), 7.00 (IH, dd, J = 9Hz, J = 2Hz), 7.02-7.11 (3H, m), 7.11-7.19 (3H, m), 7.30 (lH, d _> J = 7Hz), 7.33-7.37 (3H, m), 7.37-7.45 (2H, m), 7.46 (lH, d, J = 2Hz), 8.35 (lH, brs)

Example 11 (10)

3- (4-methylphenylthio) -1-5- (phenylenyl) indole (compound 63)

5-bromoindole 1 g, potassium carbonate 1. 8 g, copper iodide (1) 4 8 mg: triphenyl phosphine 0. 1 3 g: piste Rif enyl phosphine palladium chloride _{_{(PdC 1 2 (PPhJ 2)}} 0. 18 g of dimethoxyethane 5 m 1. Suspended in 5 ml of water and stirred at room temperature for 30 minutes. To this, 1.37 ml of ethynylbenzene was added, and the mixture was stirred at room temperature for 5 hours and at 80 for 20 hours. Water was added to the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to column chromatography (silica gel; petroleum ether Z ethyl acetate = 41) to obtain 5- (phenylethynyl) indole. The above compound was obtained in the same manner as in Example 11 (1) using this compound and bis (4-methylphenyl) disulfide.

Properties: brown powder

Melting point: 165_168 ° C

Ή-wake (CDC1 ₃ ) 6: 2.26 (3H, s), 6.99 (2Η, d, J = 9Hz), 7.03 (2H, d, J = 9Hz),

7.28-7.35 (3H, m), 7.35-7.45 (2H, m), 7.45-7.56 (3H, m), 7.85 (1H, s),

8.47 (lH, brs)

Example 1 2 (1)

5-Promote 3-Indolecarbaldehyde (Compound 64)

5.2 ml of phosphorus oxychloride was added dropwise to 20 ml of dimethylformamide at 0. A solution of 10 g of 5-bromoindole in 3 Oml of dimethylformamide was added dropwise thereto, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was added to water, 100 ml of 16% sodium hydroxide was added, and the precipitate was collected by filtration to obtain 10.26 g of the above compound.

Properties: light brown powder

Melting point: 207—2 10:

H-NMR (DMS0-d ₆ ) δ: 7.40 (1Η, d, J = 8 Hz), 7.50 (1H, d, J = 8 Hz), 8.23 (1H, s),

8.36 (1H, s), 9.93 (lH, s)

Example 12 (2)-(5)

The following (Compound 65) — (Compound 68) was obtained in the same manner as in Example 12 (1).

Example 12 (2)

4-Bromo _ 3 _Indyl carbaldehyde (Compound 65) Properties: pale yellow powder

Melting point: 184-186

_{'H-NMR (CDC1 3)} δ: 7.16 (1H, t, J = 8Hz), 7.45 (IH, d, J = 8Hz), 7.51 (IH, d, J = 8Hz), 8.11 (1H, d, J = 4Hz), 9.00 (IH, brs), 10.94 (IH, s)

Example 12 (3)

6-Promote 3-Indolecarbaldehyde (Compound 66)

Properties: brown powder

Melting point: 2 10— 2 12t

'H-NMR (DMS0-d ₆ ) δ: 7.37 (IH, dd, J = 8 Hz, 2 Hz), 7.72 (IH, d, J = 2 Hz),

8.03 (IH, d, J = 8Hz), 8.33 (IH, s), 9.94 (1H, s), 12.22 (1H, brs)

Example 1 2 (4)

5-nitro-3-indolecarbaldehyde (compound 67)

Properties: brown powder

Melting point:> 285 ° C

Ή-NMR (DMS0-d ₆ ) δ: 7.73 (IH, d, J = 9 Hz), 8.17 (IH, d, J = 9 Hz), 8.59 (IH, s), 8.95 (lH, s), 10.03 (lH , s)

Example 12 (5)

2-phenyl-3-indolecarbaldehyde (compound 68)

Properties: yellow-green powder

Melting point: 262_263 ° C

'H-NMR (DMS0-d ₆ ) δ: 7.20-7.34 (2Η, m), 7.48-7.55 (IH, m), 7.55-7.69 (3H, m), 7.71-7.81 (2H, m), 8.16- 8.27 (1H, m), 9.97 (1H, s)

Example 13 (1)

5-Bromo-3-pentafluoropropionylindole (Compound 69) 1.5 ml of pentafluoropropionic anhydride is dissolved in 5 ml of tetrahydrofuran, and a solution of 1 g of 5-bromoindole 1 g in tetrahydrofuran at 0 ° C 1 Om 1 The mixture was added dropwise and stirred at 0 ° C. for 1 hour and at room temperature for 1 day. The reaction solution was concentrated, getyl ether was added, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated. The residue was washed with hexane to obtain 1.46 g of the above compound.

Properties: colorless powder

Melting point: 226—229 ° C

_{'H-NMR (CDC1 3)} δ: 7.36 (1Η, d, J = 8Hz), 7.49 (1H, dd, J = 8Hz, J = 2Hz),

8.12 (1H, d, J = 4Hz), 8.61 (1H, d, J-2Hz), 8.98 (1H, brs)

Example 13 (2)

The following (Compound 70) was obtained in the same manner as in Example 13 (1).

5-Promote 3 _ trifluoroacetylindole (Compound 70)

Properties: brown powder

Melting point: 258—260 ° C

_{'H-NMR (CDC1 3)} δ: 7.36 (lH, d, J = 9Hz), 7.49 (1H, dd, J = 9Hz, J = 2Hz), 8.06 (1H, s), 8.59 (lH, s), 8.85 (lH, brs)

Example 14

1- (5_Bromo_3-Indolyl) —2— (4-Methyl-1-piperazinyl) ethanedione (Compound 71)

0.7 ml of oxalyl chloride was added to 5 ml of tetrahydrofuran, and a solution of 1 g of 5-bromoindole in 10 ml of tetrahydrofuran was added dropwise under ice cooling. After stirring at room temperature for 1 hour, 1.7 ml of 1-methylpiperazine was added, and the mixture was further stirred at room temperature for 1 hour. The reaction solution was concentrated, a saturated aqueous solution of sodium hydrogen carbonate was added, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to column chromatography (silica gel; chloroform-form methanol = 10-1) to obtain 1.12 g of the above compound.

Properties: yellow powder

Melting point: 195-197 ° C 'H-NMR (CDC1 ₃ ) δ: 2.33 (3H, s), 2.36-2.42 (2H, m), 2.42-2.59 (2H, m),

3.40-3.60 (2H, m), 3.60-3.83 (2H, m), 7.18 (1H, d, J-9Hz), 7.35 (1H, d, J = 9Hz), 7.7K1H, s), 8.46 (lH, s), 10.12 (lH, brs)

Example 15

5- (3-Hydroxy-3-methyl-1-butynyl) -13-Pendolecarbaldehyde (Compound 72)

0.5 g of 5-bromo-3-indole carbaldehyde, 0.78 g of potassium carbonate, 19 mg of copper (I) iodide, 48 mg of triphenylphosphine, 48 mg of 10% palladium carbon, 4 m of dimethoxyethane, 4 m of water The mixture was suspended in 1 and stirred at room temperature for 30 minutes. To this, 0.46 g of 2-methyl-3-butyn-2-ol was added, and the mixture was stirred at 80 for 1 day. The reaction solution was filtered, and the filtrate was concentrated. The residue was subjected to column chromatography (silica gel; chloroform-form methanol = 20-1) to obtain 143 mg of the above compound.

Properties: colorless powder

Melting point: 176—1 781:

'H-NMR (DMS0-d ₆ ) δ: 1.8 (6Η, s), 5.41 (IH, brs), 7.25 (IH, d, J = 9 Hz),

7.49 (IH, d, J = 9Hz), 8.12 (1H, s), 8.33 (IH, s), 9.94 (IH, s)

Example 16 (1)

5-bromo-3- (4-chlorophenylsulfonyl) —2-methylindole (Compound 73)

353 mg of 5-bromo-3- (4-chlorophenylthio) -2-methylindole was dissolved in 5 ml of dichloromethane. 435 mg of m-chloroperbenzoic acid was added to the mixture, and the mixture was stirred at room temperature for 2 days. The reaction solution was washed with 50 ml of a 1% sodium sulfite solution. The organic layer was concentrated after drying. The residue was subjected to column chromatography (silica gel; ethyl acetate ethyl form = 50Z1). Hexane was added and the mixture was filtered to obtain 12 Omg of the above compound. Properties: light brown powder

Melting point: 258—258.5 ° C

'H-NMR (DMSO-d ₆ ) δ: 2.66 (3Η, s), 7.34 (IH, dd, J = 2Hz, J = 9Hz), 7.39 (IH, d, J = 9Hz), 7.65 (2H, d, J = 9Hz), 7.93 (2H, d, J = 9Hz), 7.94 (1H, d, J = 2Hz), 12.45 (IH, brs) Example 16 (2)-(39)

The following (Compound 74) — (Compound 113) was obtained in the same manner as in Example 16 (1).

Example 16 (2)

5 _bromo- 2 _methyl _ 3— (4-methylphenylsulfonyl) indole (Compound 74)

Properties: light brown powder

Melting point: 276.5_277

'H-NMR (DMSO-d ₆ ) δ: 2.34 (3H, s), 2.66 (3Η, s),

7.32 (IH, dd, J = 2Hz, J = 9Hz), 7.37 (IH, d, J = 9Hz), 7.38 (2H, d, J = 8Hz),

7.80 (2H, d, J = 8Hz), 7.92 (IH, s), 12.34 (IH, brs)

Example 16 (3)

5-Bromo_3- (3-methoxyphenylsulfonyl) —2-methylindole (Compound 75)

Properties: brown powder

Melting point: 187—188

'H-NMR (DMS0-d ₆ ) δ 2.66 (3Η, s), 3.81 (3Η, s), 7.18 (IH, d, J = 8Hz),

7.29-7.40 (3H, m), 7.42-7.52 (2H, m), 7.94 (1H, d, J = 2Hz), 12.39 (IH, brs) Example 16 (4)

3- (benzylsulfonyl) — 5-promo 2-methylindole (Compound 76)

Properties: colorless powder Melting point: 187.5-188 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.09 (3H, s), 4.49 (2H, s), 7.02 (2H, d, J = 8Hz),

7.23 (2H, t, J = 7Hz), 7.28 (2H, dd, J = 2Hz, J = 9Hz), 7.36 (IH, d, J = 9Hz),

7.65 (1H, d, J = 2Hz), 12.18 (lH, brs)

Example 16 (5)

2-tert-butyl-5-bromo-3- (phenylsulfonyl) indole (compound 77)

Properties: brown powder

Melting point: 64-64.5 ° C

_{'H-NMR (CDC1 3)} δ: 1.61 (9Η, s), 7.25 (IH, d, J = 8Hz), 7.33 (IH, dd, J = 2Hz, J = 8Hz), 7.42-7.56 (3H, m ), 7.89 (2H, dd, J = 2Hz, J = 8Hz), 8.31 (1H, d, J = 2Hz), 10.87 (IH, brs) Example 16 (6)

3- (4-chlorophenylsulfonyl) -1,2,5-dimethylindole (Compound 78)

Properties: brown powder

Melting point: 101-103 ° C

_{'H-NMR (CDC1 3)} δ: 2.47 (3Η, s), 2.73 (3Η, s), 7.06 (IH, dd, J = 2Hz, J = 8Hz), 7.20 (lH, d, J = 8Hz)> 7.42 (2H, dd, J = 2Hz, J = 8Hz), 7.80 (IH, s),

7.92 (2H, dd, J = 2Hz, J = 8Hz), 8.44 (IH, brs)

Example 16 (7)

(2-methyl-3- (phenylsulfonyl) indole-5-yl) ethyl acetate (Compound 79)

Properties: light brown powder

Melting point: 11 1 _ 1 12 ° C

'H-NMR (DMS0-d ₆ ) <5: 1.24 (3H, t, J = 7 Hz), 2.59 (3H, s), 3.68 (2H, s),

4.12 (2H, q, J = 7Hz), 7.03 (2H, t, J = 8Hz), 7.35-7.47 (3H, m), 7.87 (IH, s), 7.91 (2H, d, J = 8Hz), 8.89 (lH, brs)

Example 16 (8)

2-Methyl-3-phenylsulfonylindole-1-ethyl carboxylate (Compound 80)

Properties: yellow powder

Melting point: 197.5-198 ° C

'H-NMR (DMSO-d ₆ ) δ: 1.35 (3Η, t, J = 7 Hz), 2.69 (3H, s), 4.34 (2H, q, J = 7 Hz), 7.49 (1H, d, J = 9 Hz) ), 7.55-7.65 (3H, m), 7.81 (IH, dd, J = 2Hz, J = 9Hz),

7.89 (2H, dd, J = 2Hz. J = 9Hz), 8.51 (1H, s)

Example 16 (9)

5 _Bromo-2-methyl-3-phenylsulfonylindole (Compound 81) Properties: Light brown powder

Melting point: 205— 205.5

'H-NMR (DMSO-de) δ: 2.67 (3Η, s), 7.33 (IH, dd, J = 2Hz, J = 9Hz),

7.38 (1H, d, J = 8Hz), 7.59 (IH, d, J = 8Hz), 7.63 (2H, dd, J = 2Hz, J = 8Hz),

7.91-7.95 (3H, m), 12.39 (IH, brs)

Example 16 (10)

5-Bromo _3 _ (4-chlorophenylsulfonyl) —2-ethylindole (Compound 82)

Properties: pale yellow powder

Melting point: 204 _ 204.5:

'H-NMR (CDCl ₃ + DMSO-d ₆ ) δ: 1.3K3H, t, J = 8Hz), 3.13 (2H, q, J = 8Hz),

7.24 (1H, t, J = 8Hz), 7.28 (lH, t, J = 8Hz), 7.42 (2H, dd, J = 2Hz, J = 9Hz),

7.87 (2H, dd, J = 2Hz, J = 9Hz), 8.14 (1H, d, J = 2Hz), 11.33 (1H, brs)

Example 16 (1 1)

5-cyano 2-methyl-3-phenylsulfonylindole (Compound 83) Properties: pale red powder

Melting point: 1 19-1 120 ° C

'H-NMR (DMSO-d ₆ ) δ: 2.70 (3Η, s), 7.52-7.65 (5Η, m), 7.99 (2Η, dd, J = 2Hz, J = 8Hz), 8.23 (lH, s)

Example 16 (12)

5-Bromo_2,7-dimethyl-3-phenylsulfonylindole (compound 84)

Properties: brown oil

_{'H-NMR (CDC1 3)} δ: 2.41 (3Η, s), 2.74 (3Η, s), 7.13 (IH, d, J = 2Hz),

7.42-7.53 (3H, m), 7.95 (2H, dd, J = 2Hz, J = 7Hz), 8.03 (IH, s), 8.47 (IH, s) Example 16 (13)

(5-bromo_3_ (4-chlorophenylsulfonyl) indole-2-yl) acetic acid ethyl ester (compound 85)

Properties: pale yellow oil

_{'H-NMR (CDC1 3)} δ: 1.23 (3Η, t, J = 8Hz), 2.59 (3H, s), 4.11 (2H, q, J = 8Hz),

6.98-7.07 (2H, m), 7.35-7.48 (3H, m), 7.87 (IH, s), 7.92 (2H, d, J = 8Hz),

8.89 (lH, brs)

Implementation 16 (14)

2_Methyl-5_trifluoromethyl_3-Phenylsulfonylindole (Compound 86)

Properties: colorless powder

Melting point: 241-242 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.71 (3Η, s), 7.51 (IH, d, J = 9Hz), 7.55-7.68 (4H, m),

7.92 (2H, dd, J = 2Hz, J = 7Hz), 8.14 (1H, s)

Example 16 (15)

5-Acetyl-2-methyl-3-phenylsulfonylindole (Compound 87) Properties: yellow powder

Melting point: 231.5-233.5 ° C

_{'H-NMR (CDC1 3)} δ: 2.67 (3Η, s), 2.71 (3H, s), 7.29 (IH, dd, J = 2Hz, J = 8Hz), 7.36-7.52 (4H, m), 7.83 ( IH, d, J = 8Hz), 7.95 (2H, d, J = 7Hz), 8.62 (1H, s) Example 16 (16)

(2-Methyl-3-phenylsulfonylindole-5-yl) Benzyl acetate (Compound 88)

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ 2.67 (3Η, s), 3.79 (2Η, s), 5.15 (2H, s), 7.05-7.15 (2H, m), 7.32-7.50 (8H, m), 7.94 ( 2H, s), 7.96 (IH, s), 8.59 (IH, brs)

Example 16 (17)

2-Methyl-3-phenylsulfonyl-5- (phenylsulfonylmethyl) indole (Compound 89)

Properties: colorless powder

Melting point: 260—261 ° C

Ή-NMR (DMS0-d ₆ ) δ 2.62 (3Η, s), 4.78 (2H, s), 7.00 (IH, d, J = 8.5 Hz),

7.28 (IH, d, J = 8.5Hz), 7.50-7.80 (9H, m), 7.82 (2H, d, J = 8. OHz), 12.20 (1H, brs) Example 16 (18)

5-cyanomethyl-2-methyl-3-phenylsulfonylindole (Compound 90)

Properties: pale yellow solid

Melting point: 204— 204.5 ° C

Ή-NMR (DMS0-d ₆ ) δ 2.67 (3Η, s), 4.12 (2H, s), 7.15 (1H, dd, J = 2 Hz, J = 8.5 Hz), 7.46 (IH, d, J = 8.5 Hz) ), 7.52-7.65 (3H, m), 7.86 (1H, s),

7.92 (2H, dd, J = 2Hz, J = 8.5Hz), 12.20 (IH, brs)

Example 16 (19) 2-Methyl-3-phenylsulfonylindole-5-benzylbenzene ester (Compound 91)

Properties: pale red powder

Melting point: 195.5-196 ° C

'H-NMR (DMSO-d ₆ ) δ 2.70 (3Η, s), 5.39 (2H, s), 7.36-7.39 (1H, m),

7.44 (2H, t, J = 8Hz), 7.49-7.55 (3H, m), 7.57-7.63 (3H, m),

7.84 (1H, dd, J = 1 Hz, J = 8 Hz), 7.90 (2H, d, J = 8 Hz), 8.54 (1H, s)

Example 16 (20)

5 Benzylsulfonylmethyl-2-methyl-3-phenylsulfonylindole (Compound 92)

Properties: pale yellow powder

Melting point: 202- 203

_{'H-NMR (CDC1 3)} δ: 2.69 (3Η, s), 4.06 (2Η, s), 4.21 (2H, s), 7.21-7.31 (IH, m), 7.34-7.46 (9H, m), 7.93 (2H, dd, J = 2Hz, J = 8Hz), 7.98 (1H, s), 10.63 (IH, brs) Example 16 (21)

2- (2-Methyl-3-phenylsulfonylindole-5-methylmethylsulfonyl) benzoic acid methyl ester (Compound 93)

Properties: yellow powder

Melting point: 108 _ 109 ° C

_{'H-NMR (CDC1 3)} δ: 2.64 (3Η, s), 4.06 (3Η, s), 4.85 (2Η, s), 7.09 (IH, d, J = 8Hz), 7. lKlH.d, J = 8Hz), 7.36 (1H, d, J = 8Hz), 7.41-7.48 (3H, m), 7.56 (IH, d, J = 8Hz), 7.60 (IH, d, J = 8Hz), 7.69 (IH, d , J = 8Hz), 7.90 (3H, d, J = 8Hz), 8.77 (IH, brs) Example 16 (22)

5-tert-butoxycarbonylamino-2-methyl-3- (2-pyridylsulfonyl) indole (Compound 94)

Properties: pale yellow powder Melting point: 155—157 ° C

'Η— 刚 R (DMS0-d ₆ ) (5: 1.47 (9H, s), 2.66 (3H, s), 7.24 (2H, d, J = 9Hz),

7.59 (IH, dd, J = 4Hz, J = 8Hz), 7.96 (1H, s), 8.08-8.11 (2H, m), 8.62 (1H, d, J = 4Hz), 9.17 (lH, brs), 12.06 (lH, brs)

Example 16 (23)

3- (2-Methyl-3_phenylsulfonylindole-5%) _ 2,4 (IH, 3H) -quinazolinedione (Compound 95)

Properties: light brown powder

Melting point: 296—299

'H-NMR (DMS0-d ₆ ) δ: 2.73 (3Η, s), 7.11 (IH, d, J = 8Hz), 7.23-7.27 (2H, m), 7.47 (IH, d, J = 8Hz), 7.55 (2H, d, J = 8Hz), 7.60-7.63 (1H, m), 7.72 (IH, t, J = 8Hz), 7.76 (1H, s), 7.86-7.97 (3H, m), 11.5 (1H , S), 12.33 (IH, s)

Example 16 (24)

5-Acetylamino-3-phenylsulfonylindole (Compound 96) Properties: Light brown powder

Melting point: 1 19- 120

'H-NMR (DMS0-d ₆ ) δ: 2.04 (3H, s), 7.40 (1H, d, J = 9 Hz),

7.48 (IH, dd, J = 2Hz, J = 9Hz), 7.55-7.60 (3H, m), 7.93 (2H, dd, J = 2Hz, J = 8Hz), 8.08 (lH, d, J = 2Hz), 8.12 (IH, s), 9.94 (IH, s), 11.80 (IH, brs)

Example 16 (25)

5-benzoylamino-3-phenylsulfonylindole (compound 97) Properties: brown powder

Melting point: 89_911

'H-NMR (DMS0-d ₆ ) δ: 7.46 (IH, d, J = 9 Hz), 7.52-7.59 (6H, m), 7.70 (IH, d, J = 9 Hz), 7.96-8.00 (4H, m ), 8.15 (1H, s), 8.28 (1H, s), 10.29 (1H, s), 12.25 (1H, s) Example 16 (26) N- (3-Phenylsulfonylindole-5-yl) — N '—Phenylperia (Compound 98)

Properties: brown powder

Melting point: 242—243 ° C

'H-NMR (DMSO-d ₆ ) δ: 6.96 (1H, t, J = 8 Hz), 7.26-7.31 (3H, m), 7.40 (IH, d, J = 9 Hz),

7.46 (2H, d, J = 8Hz), 7.56-7.60 (3H, m), 7.94 (3H, d, J = 6Hz), 8.11 (IH, d, J = 3Hz),

8.56 (1H, s), 8.70 (lH, s), 12.17 (lH, s)

Example 16 (2 7)

3-Phenylsulfonyl-5- (4-toluenesulfonylamino) indole (Compound 99)

Properties: blue powder

Melting point: 210-212 ° C

'H-NMR (DMSO-d ₆ ) δ: 2.30 (3Η, s), 6.99 (IH.dd.J = 2Hz, J-9Hz),

7.27 (2H, d, J = 9Hz), 7.34 (IH, d, J = 9Hz), 7.52-7.63 (5H, m), 7.64 (IH, t, J = 8Hz), 7.86 (2H, d, J = 8Hz), 8.12 (1H, s), 10.06 (IH, brs), 12.21 (1H, brs)

Example 16 (28)

5-tert-butoxycarbonylamino _ 3 _phenylsulfonylindole (compound 100)

Properties: green powder

Melting point: 2 2 2.5-2 2 3t:

Ή-NMR (DMS0-d ₆ ) δ: 1.49 (9Η, s), 7.35 (2H, d, J = 9Hz), 7.54-7.59 (3H, m),

7.89-7.96 (3H, m), 8.08 (IH, d, J = 4Hz), 9.28 (IH, brs), 12.13 (1H, brs)

Example 16 (29)

5-Promo 3-Methanesulfonyl 2-methylindole (Compound 101) Properties: Brown powder

Melting point: 2 1 1 _ 2 13 ° C Ή-NMR (DMS0-d ₆ ) δ 2.61 (3H, s), 3.13 (3H, s), 7.32 (IH, dd, J = 2 Hz, J = 8 Hz), 7.39 (lH, d, J = 8 Hz), 7.89 (lH, d, J = 2Hz), 12.29 (lH, brs)

Example 16 (30)

3- (3-Phenylsulfonylindole-5-yl) —2,4 (IH, 3H) -quinazolinedione (Compound 102)

Properties: blue powder

Melting point: 2 17—218 ° C

Ή-NMR (DMS0-d ₆ ) δ: 7.17 (1H, d, J = 9 Hz), 7.23 (2H, t, J = 9 Hz), 7.53-7.60 (4H, m),

7.70 (1H, t, J = 8Hz), 7.94 (IH, s), 7.95 (IH, d, J = 8Hz), 7.99 (2H, d, J = 8Hz),

8.29 (1H, s), 11.54 (lH, brs), 12.44 (lH, brs)

Example 16 (31)

2,5-Dimethyl-3-phenylsulfonylindole (Compound 103) Properties: Light brown powder

Melting point: 164_166 ° C

_{'H-NMR (CDC1 3)} δ: 2.49 (3H, s), 2.76 (3H, s), 7.07 (IH, d, J = 8Hz),

7.21 (IH, d, J = 8Hz), 7.30-7.54 (3H, m), 7.87 (IH, s), 8.01 (2H, dd, J = 2Hz, J = 8Hz), 8.42 (lH, brs)

Example 16 (32)

5-bromo-3-phenylsulfonylindole (compound 104)

Properties: colorless powder

Melting point: 1 79-182 t

_{'H-NMR (CDC1 3)} δ 7.24-7.42 (2Η, m), 7.42-7.60 (3Η, m), 7.84-7.91 (IH, m), 7.96-8.10 (3H, m), 9.15 (1H, brs )

Example 16 (33)

5-bromo-3-phenylsulfinylindole (Compound 105)

Properties: colorless powder Melting point: 117-119C

_{'H-NMR (CDC1 3)} δ: 7.13 (1H, d, J = 9Hz), 7.23 (1H, dd, J = 9Hz, 2Hz),

7.46-7.60 (5H, m), 7.68 (2H, dd, J = 8Hz, J = 2Hz), 9.87 (IH, brs)

Example 16 (34)

3— (4-Methylphenylsulfonyl) — 5_ (phenylenetin) indole (Compound 106)

Properties: brown powder

Melting point: 182-185 ° C

_{'H-NMR (CDC1 3)} δ: 2.37 (3Η, s), 7.25-7.30 (2Η, m), 7.30-7.40 (4Η, m),

7.43 (1Η, d, J = 5Hz), 7.56 (2Η, dd, J = 7Hz, J = 2Hz), 7.88 (IH, d, J = 3Hz),

7.92 (2H, d, J = 8Hz), 8.12 (IH, s), 9.04 (IH, brs)

Example 16 (35)

5-benzyloxy-3- (4-methylphenylsulfonyl) indole (Compound 107)

Properties: green powder

Melting point: 132-135

_{'H-NMR (CDC1 3)} δ: 2.35 (3Η, s), 5.11 (2Η, s), 6.97 (IH, dd, J = 8Hz, J = 2Hz), 7.20 (2H, d, J = 3Hz), 7.27 (1H, d, J = 9Hz), 7.33-7.38 (IH, m), 7.38-7.44 (3H, m), 7.46 (2H, d, J = 8Hz), 7.78 (IH, d, J = 3Hz) , 7.81 (2H, d, J = 8Hz), 8.85 (IH, brs) Example 16 (36)

5-benzyloxy-3-phenylsulfonylindole (compound 108) Properties: green powder

Melting point: 141-143 X:

_{'H-NMR (CDC1 3)} δ: 5.12 (2Η, s), 6.98-7.02 (IH, m), 7.22-7.32 (2Η, m),

7.32-7.51 (8H, m), 7.80 (IH, d, J = 3Hz), 7.90-7.96 (2H, m), 8.89 (1H, brs) Example 16 (37) 2- (5-bromo_2-methylindole-3-ylsulfonyl) benzyl benzoate (Compound 109)

Properties: light brown powder

Melting point: 168-170 ° C

_{'H-NMR (CDC1 3)} δ 2.62 (3Η, s), 5.36 (2Η, s), 6.99 (1Η, d, J = 9Hz),

7.20-7.25 (1H, m), 7.30-7.39 (3H, m), 7.43 (2H, d, J = 7Hz), 7.50-7.60 (3H, m), 8.00-8.07 (2H, m), 8.57 (lH , brs)

Example 16 (38)

5-benzoyl_2-methyl-3-phenylsulfonylindole (compound 110) and 5-benzoyl-2-methyl-3-phenylsulfinylindole (compound 111)

The reaction was carried out in the same manner as in Example 16 (1) using 5-benzoyl-2-methyl-3-phenylthioindole. The reaction solution was washed three times with 5% of a 3% sodium sulfite solution. The insolubles at this time were filtered. The organic layer was concentrated after drying. Ether was added and the mixture was filtered to obtain a sulfonyl compound. The filtered solid was washed with water, ethanol and hexane to obtain a sulfinyl compound.

Compound 1 10

Properties: pale yellow powder

Melting point: 211.5-212 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.73 (3Η, s), 7.55 (1Η, d, J = 9 Hz), 7.58-7.75 (9H, m), 7.87 (2H, d, J = 8 Hz), 8.23 (1H, s), 12.60 (1H, brs)

Compound 1 1 1

Properties: colorless powder

Melting point: 157.5—158 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.73 (3Η, s), 7.42 (2Η, d, J = 9 Hz), 7.46-7.65 (10H, m), 7.66 (lH, d, J = 8 Hz), 12.30 (lH, brs) Example 16 (39)

5-Promote 3- (4-hydroxyphenylsulfonyl) -12-methylindole (compound 112) and 5-bromo-3- (4-hydroxyphenylsulfinyl) _2-methylindole (compound 1 1 3)

The reaction was carried out in the same manner as in Example 16 (1) using 5-bromo-2-methyl-3- (4-hydroxyphenylthio) indole. The reaction solution was washed three times with 50 ml of a 3% sodium sulfite solution. The insolubles at this time were filtered. The organic layer was concentrated after drying. Ether was added and the mixture was filtered to obtain a sulfonyl compound. The filtered solid was washed with water, ethanol and hexane to obtain a sulfinyl compound.

Compound 1 12

Properties: brown powder

Melting point: 238. 5— 239. 5:

_{'Η - NMR (DMS0- d 6} ) 6: 2.64 (3H, s), 6.89 (2Η, d, J = 8Hz), 7.31 (IH, d, J = 8Hz), 7.36 (IH, d, J = 8Hz ), 7.74 (2H, d, J = 8Hz), 7.93 (IH, s), 10.44 (1H, s),

12.27 (1H, s)

Compound 1 13

Properties: brown powder

Melting point: 1 17.5-1-18.5 ° C

Ή-1 NMR (DMS0-d ₆ ) δ: 2.63 (3Η, s), 6.90 (2Η, dd, J = 2Hz, J = 9Hz),

7.20 (IH, dd, J = 2Hz, J = 9Hz), 7.27 (IH, d, J = 2Hz), 7.33 (IH, d, J = 9Hz),

7.41 (2H, d, J = 9Hz), 9.96 (IH, s), 11.99 (IH, s)

Example 17 (1)

2-Methyl-6-nitro-3-phenylsulfonylindole (Compound 114) and 2-Methyl-4,2-nitro-3-phenylsulfonylindole (Compound 115)

Example 3 using 3-nitroaniline and 1-phenylthio-2-propanone (1) A 1: 1 mixture of 2-methyl-4-nitro-13-phenylthioindole and 2-methyl-6-nitro-3-phenylthioindole as yellow powder was obtained in the same manner. Using this mixture, the above compound mixture was obtained in the same manner as in Example 16 (1). The residue was subjected to column chromatography (silica gel; chromate form Z ethyl acetate = 10 / \). Since the 6-nitro form eluted first, the 4-nitro form eluted. Hexane was added and filtered.

Compound 1 1 5

Properties: yellow powder

Melting point: 207.5 _ 209

'H-NMR (CDCl ₃ + DMSO-d ₆ ) δ: 2.75 (3Η, s), 7.44-7.55 (3Η, s),

7.94 (2H, dd, J = 2Hz, J = 7Hz), 8.08 (IH, dt, J = 2Hz, J = 8Hz),

8.10 (lH, dd, J = 2Hz, J = 8Hz), 8.26 (IH, d, J = 2Hz), 12.02 (IH, brs)

Compound 1 16

Properties: yellow powder

Melting point: 239-240

'H-NMR (CDCl ₃ + DMSO-d ₆ ) <5: 2.87 (3H, s), 7.22 (IH, t, 8Hz), 7.48-7.57 (4H, m), 7.59 (IH, dd, J = lHz , J = 9Hz), 7.95 (IH, dd, J = 1Hz, J = 9Hz), 12.08 (1H, brs) Example 17 (2) 1 (3)

Example 1 The following (Compound 116) — (Compound 118) were obtained in the same manner as in (1).

Example 17 (2)

2-Methyl-3-phenylsulfonylindole 6-carboxylate (Compound 116)

Properties: yellow powder

Melting point: 20 1-202 ° C

_{'H-NMR (CDC1 3)} δ 1.40 (3H, t, J = 7Hz), 2.78 (3Η, s), 4.39 (2Η, q, J = 7Hz), 7.42-7.53 (3H, m) 7.92 (lH, dd, J = 2Hz, J = 8Hz), 7.97 (2H, dd, J = 2Hz, J = 8Hz),

8.06 (IH, d, J = 2Hz), 8.08 (IH, d, J = 8Hz), 8.97 (IH, brs)

2-Methyl-3-phenylsulfonylindole-1-ethyl carboxylate (Compound 1 17)

Properties: yellow powder

Melting point: 134.5-136.5 ° C

_{'H-NMR (CDC1 3)} δ 1.26 (3H, t, J = 7Hz), 2.56 (3H, s), 4.29 (2H, q, J-7Hz), 7.17 (IH, t, J = 8Hz), 7.31 (IH, dd, J = lHz, J = 8Hz), 7.35 (IH, dd, J = lHz, J = 8Hz), 7.41-7.51 (3H, m), 7.92 (IH, d, J = 2Hz), 7.93 (IH, d, J = 8Hz), 9.45 (IH, brs) Example 1 7 (3)

(2-Methyl-3-phenylsulfonylindole_4_yl) Methyl ester (Compound 1 18)

Properties: brown oil

_{'H-NMR (CDC1 3)} δ: 2.69 (3Η, s), 3.67 (5Η, brs), 7.12 (1H, d, J = 8Hz),

7.15 (1H, s), 7.40-7.51 (3H, m), 7.96 (3H, d, J = 6Hz), 8.78 (IH, brs)

Example 18 (1)

5-Bromo 1- (4-chlorobenzoyl) 1-3- (4-chlorophenylsulfonyl) 1-2-methylindole (Compound 1 19)

5-Bromo-3- (4-chlorophenylsulfonyl) -2-methylindole l O Omg was added little by little to 5 ml of tetrahydrofuran solution of 16 mg of sodium hydride (60%) under ice-cooling. . After stirring for 20 minutes, 75 mg of 4-chlorobenzoyl chloride and 5 mg of 4-dimethylaminopyridine were added, and the mixture was stirred at the same temperature for 90 minutes. The solvent was distilled off under reduced pressure. To the residue was added 3 Oml of chloroform in form, and the mixture was washed with 1% aqueous sodium hydrogen carbonate and 1% aqueous citric acid. The organic layer was concentrated after drying. The residue was subjected to column chromatography (silica gel; chromate form). Hexane was added to the residue, followed by filtration to obtain 106 mg of the above compound. Properties: colorless powder

Melting point: 1 6 2— 1 63.5 ° C

Ή-NMR (CDCI3) δ 2.72 (3Η, s), 6.80 (IH, d, J = 9Hz), 7.25 (1H, dd, J = 2Hz, J = 9Hz),

7.49 (4H, dd, I = 3Hz, J = 9Hz), 7.65 (2H, d, J = 9Hz), 7.93 (2H, d, J = 9Hz),

8.31 (lH, d, J = 2Hz)

Example 18 (2)-(5 3)

The following (Compound 120)-(Compound 1771) were obtained in the same manner as in Example 18 (1).

Example 18 (2)

5-Bromo _ 1 _ (4-methylbenzoyl) _ 2-methyl-3- (4-methylphenylsulfonyl) indole (Compound 120)

Properties: colorless powder

Melting point: 10.5-181.5 ° C

'.Eta. thigh _{(CDC1 3) δ: 2.41 (} 3H, s), 2.72 (3H, s), 6.80 (lH.d, J = 9Hz),

7.24 (IH, dd, J = 2Hz, J = 9Hz), 7.32 (2H, d, J = 9Hz), 7.50 (2H, d, J = 9Hz),

7.64 (2H, d, J = 9Hz), 7.88 (2H, d, J = 9Hz), 8.33 (1H, d, J = 2Hz)

Example 18 (3)

3-(benzylsulfonyl) _ 5 _ bromo-1-(4-chlorobenzoyl) 1-2-methylindole (Compound 1 2 1)

Properties: colorless powder

Melting point: 14 1 1 1 4 1.5 ° C

Awake (CDC1 ₃ ) δ: 2.02 (3Η, s), 4.39 (2H, s), 6.89 (IH, d, J = 9Hz),

7.06 (2H, d, J = 7Hz), 7.21-7.35 (4H, m), 7.49 (2H, d, J = 9Hz), 7.56 (2H, d, J = 9Hz),

8.08 (lH, s)

Example 18 (4)

5—Bromo 1— (4 benzoyl) 1 3_ (3—Methoxyphenylsul) Fonyl) 1-Methylindole (Compound 122)

Properties: colorless powder

Melting point: 215.5-216 ° C

_{'H-NMR (CDC1 3)} δ: 2.73 (3Η, s), 3.85 (3H, s), 6.80 (1H, d, J = 9Hz),

7.09 (1H, dd, J = 2Hz, J = 8Hz), 7.24 (1H, dd, J = 2Hz, J = 8Hz),

7.42 (1H, dd, J = 2Hz, J = 8Hz), 7.47-7.58 (4H, m), 7.65 (2H, d, J = 8Hz),

8.34 (lH, d, J = 2Hz)

Example 18 (5)

{1-(4_ benzoyl) —2-methyl-3-phenylsulfonylindo —lu-5-yl} Ethyl acetate (Compound 123)

Properties: colorless amorphous

Melting point: 54—54.5X

_{'H-NMR (CDC1 3)} δ: 1.26 (3H, t, J = 7Hz), 2.74 (3Η, s), 3.72 (2Η, s),

4.16 (2H, q, J = 7Hz), 6.86 (1H, d, J = 9Hz), 7.09 (1H, d, J = 2Hz, J = 9Hz),

7.46-7.58 (5H, m), 7.66 (2H, d, J = 9Hz), 8.01 (2H, dd, J = 2Hz, J = 9Hz), 8.09 (1H, s) Example 18 (6)

5-Bromo _ 1- (4-Dimethylaminobenzoyl) -3-Methanesulfonyl 2-methylindole (Compound 124)

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ: 2.72 (3H, s), 3.12 (6H, s), 3.15 (3H, s), 6.64 (2H, d, J = 8Hz), 6.99 (1H, d, J = 8Hz), 7.23-7.29 (1H, m), 7.59 (2H, d, J = 8Hz), 8.18 (1H, s) Example 18 (7)

1- (4-cyclobenzoyl) —3- (4-chlorophenylsulfonyl) —2,5-dimethylindole (Compound 125)

Properties: colorless powder

Melting point: 167—168 ° C 'Η-Maraudal R (CDC1 ₃ ) δ: 2.44 (3Η, s), 2.74 (3Η, s), 6.76 (IH, d, J = 8Hz),

6.95 (1H, d, J = 8Hz), 7.26-7.49 (4H, m), 7.66 (2H, dd, J = 2Hz, J = 8Hz), 7.91 (IH, s), 7.94 (2H, dd, J = (2Hz, J = 8Hz)

Example 18 (8)

1- (4-methylbenzoyl) -2-methyl-6-2-nitro-3-phenylsulfonylindole (Compound 126)

Properties: colorless powder

Melting point: 159.5-160.5

_{'H-NMR (CDC1 3)} δ: 2.75 (3Η, s), 7.55 (4Η, d, J = 8Hz), 7.61 (IH, t, J = 8Hz),

7.68 (2H, d, J = 9Hz), 7.99 (3H, t, J = 8Hz), 8.21 (IH, d, J = 9Hz), 8.33 (IH, d, J = 9Hz) Example 18 (9)

1-1- (4-methylbenzoyl) -1-2-Methyl_4_Nitro-3_Phenylsulfonylindole (Compound 127)

Properties: pale yellow powder

Melting point: 210 _ 21 1 ° C

_{'H-NMR (CDC1 3)} δ: 2.80 (3Η, s), 7.21 (2Η, d, J = 8Hz), 7.42-7.61 (6H, m), 7.68 (2H, d, J = 9Hz), 7.95 ( (2H, d, J = 9Hz)

Example 18 (10)

1- (4-Benzoyl) 1 2 _methyl _ 3 -Phenylsulfonylindole 1 -6-Ethyl ruvonate (Compound 128)

Properties: colorless powder

Melting point: 142.5—143 ° C

_{'H-NMR (CDC1 3)} 6: 1.3K3H, t, J = 7Hz), 2.76 (3H, s), 4.29 (2H, q, J = 7Hz), 7.49-7.61 (5H, m), 7.66 (1H , S), 7.68 (2H, dd, J = 2Hz, J = 9Hz),

7.99 (1H, dd, J = 2Hz, J = 9Hz), 8.01 (2H, d, J = 8Hz), 8.22 (IH, d, J = 9Hz)

Example 18 (1 1) 1- (4-methylbenzene) _ 2-Methyl-3-phenylsulfonylindole 4 _Ethyl carboxylate (Compound 129)

Properties: pale yellow powder

Melting point: 161.5-162.5 ° C

_{'H-NMR (CDC1 3)} δ: 1.32 (3H, t, J = 7Hz), 2.64 (3H, s), 4.38 (2H, q, J = 7Hz), 7.09 (IH, d, J = 8Hz), 7.19 (IH, t, J-8Hz), 7.40 (1H, d, J = 7Hz), 7.48-7.61 (5H, m), 7.67 (2H, d, J = 8Hz), 8.05 (2H, d, J = 8Hz)

Example 18 (12)

1- (4-Benzoyl) — 2-Methyl-3-phenylsulfonylindole 5-5-Ethyl rubonate (Compound 130)

Properties: colorless powder

Melting point: 192.5-1 94t:

_{'H-NMR (CDC1 3)} δ: 1.42 (3Η, t, J = 7Hz), 2.77 (3H, s), 4.41 (2H, q, J = 7Hz),

6.95 (IH, d, J = 9 Hz), 7.45-7.62 (5H, m), 7.67 (2H, d, J = 8 Hz), 7.85 (IH, d, J = 8 Hz), 8.04 (2H, d, J = 8Hz), 8.85 (1H, s)

Example 18 (13)

5_Bromo_3 -— (4-chlorophenylsulfonyl) -1-1 (4-benzobenzene) -1-2-ethylindole (Compound 131)

Properties: colorless powder

Melting point: 126— 126.5

'Η-Sub R (CDC13) δ: 1.17 ( ₃ (, t, J = 8Hz), 3.26 (2H, q, J = 8Hz), 6.62 (IH, d, J = 9Hz),

7.21 (IH, dd, J = 2Hz, J = 9Hz), 7.49-7.53 (4H, m), 7.64 (2H, dd, J = 2Hz, J = 9Hz), 7.94 (2H, dd, J = 2Hz, J = 9Hz), 8.31 (IH, d, J = 2Hz)

Example 18 (14)

1-1- (4-methylbenzoyl) -1-5-cyano_2-methyl-3-3-phenylsulfonylindole (Compound 132) Properties: yellow powder

Melting point: 199.5-200.5:

_{'H-NMR (CDC1 3)} δ: 2.75 (3Η, s), 7.05 (IH, d, J = 9Hz), 7.41 (IH, d, J = 8Hz), 7.50-7.68 (7H, m), 7.99 ( 2H, d, J = 8Hz), 8.55 (1H, s)

Example 18 (15)

5_bromo_1- (4-dimethylaminobenzoyl) _ 2 _methyl-3-phenylsulfonylindole (Compound 133)

Properties: yellow amorphous

Melting point: 68- 69

_{'H-NMR (CDC1 3)} δ: 2.71 (3Η, s), 3.14 (6Η, s), 6.64 (2Η, d, J = 9Hz),

6.94 (1H, d, J = 9Hz), 7.23 (1H, dd, J = 2Hz, J = 8Hz), 7.49-7.58 (4H, m),

7.91 (IH, d, J = 9Hz), 8.00 (2H, d, J = 8Hz), 8.32 (IH, d, J = 2Hz)

Example 18 (16)

(1-(4-Benzoyl) _ 2 -Methyl _ 3 -Phenylsulfonylindia 1 -4-yl) Methyl acetate (Compound 134)

Properties: colorless oil

_{'H-NMR (CDC1 3)} δ: 2.71 (3Η, s), 3.57 (2Η, s), 3.62 (3Η, s), 6.91 (IH, s),

7.22 (IH, d, J = 8Hz), 7.48-7.59 (5H, m), 7.67 (2H, d, J = 8Hz), 8.00 (2H, d, J = 8Hz), 8.ll (lH, d, (J = 8Hz)

Example 18 (17)

5-Bromo-2-methyl-1- (2-methylbenzoyl) _ 3 _phenylsulfonylindole (Compound 135)

Properties: colorless powder

Melting point: 149-1 149.5 in

_{'H-NMR (CDC1 3)} δ: 2.34 (3Η, s), 2.65 (3Η, s), 6.83 (IH, d, J = 9Hz),

7.23 (IH, d, J = 9Hz), 7.27 (2H, d), 7.36 (1H, d, J = 8Hz), 7.48-7.62 (4H, m), 7.98 (2H, d, J = 8Hz), 8.34 (1H, s)

Example 18 (18)

2-Methyl-11- (2-methylbenzoyl) _ 3 _phenylsulfonyl-5-trifluoromethylindole (Compound 136)

Properties: colorless powder

Melting point: 1 10—1 10.5 ° C

_{'H-NMR (CDC1 3)} 6: 2.38 (3H, s), 2.69 (3Η, s), 7.05 (IH, d, J = 9Hz),

7.27 (2H, dd, J = 4Hz, J = 7Hz), 7.38 (2H, dd, J = 4Hz, J = 7Hz), 7.50-7.61 (4H, m), 7.99 (2H, d, J = 8Hz), 8.48 (lH, s)

Example 18 (19)

1- (4-benzobenzene) _ 2 _methyl _ 3 _phenylsulfonyl-5-trifluoromethylindole (Compound 137)

Properties: colorless powder

Melting point: 169-170

_{'H-NMR (CDC1 3)} 6: 2.76 (3H, s), 7.04 (IH, d, J = 9Hz), 7.40 (IH, d, J = 9Hz), 7.49-7.64 (5H, m), 7.66 ( 2H, d, J = 8Hz), 8.01 (2H, d, J = 8Hz), 8.49 (1H, s) Example 18 (20)

5 _Benziru-2-methyl-1 _ (2-methylbenzoyl) -3-phenylsulfonylindole (Compound 138)

Properties: yellow powder

Melting point: 142-144:

_{'H-NMR (CDC1 3)} δ: 2.41 (3Η, s), 2.76 (3H, s), 7.03 (IH, d, J = 9Hz),

7.29 (2H, d, J = 7Hz), 7.39 (1H, d, J = 7Hz), 7.48-7.67 (8H, m),

7.78 (2H, dd, J = 2Hz, J = 8Hz), 7.95 (2H, dd, J = 2Hz, J = 8Hz), 8.52 (1H, d, J = 2Hz) Example 18 (21)

5 _ Benzyl — 1— (4-chlorobenzoyl) — 2-methyl — 3-phenyl Ruphonylindole (Compound 139)

Properties: yellow amorphous

Melting point: 74- 75

_{'H-NMR (CDC1 3)} δ: 2.81 (3Η, s), 7.03 (IH, d, J = 9Hz), 7.42-7.72 (1 IH, m), 7.79 (2H, dd, J = 2Hz, J = 7 Hz), 7.97 (2H, dd, J = 2Hz, J = 7Hz), 8.53 (1H, d, J-2Hz) Example 18 (22)

5-Acetyl-2-methyl-11- (2-methylbenzoyl) _ 3 _phenylsulfonylindole (Compound 140)

Properties: pale red powder

Melting point: 1 78— 1 79.5 ° C

_{'H-NMR (CDC1 3)} 6: 2.38 (3H, s), 2.68 (3Η, s), 2.71 (3H, s), 6.98 (IH, d, J = 9Hz), 7.28 (2H, d, J = 9Hz), 7.38 (IH, d, J = 8Hz), 7.48-7.62 (4H, m),

7.77 (IH, dd, J = 2Hz, J = 9Hz), 8.01 (2H, d, J = 8Hz), 8.76 (IH, s)

Example 18 (23)

5-Acetyl—1 _ (4-chlorobenzoyl) —2-Methyl-3-phenylsulfonylindole (Compound 141)

Properties: pale red powder

Melting point: 18 1.5-183.5 ° C

_{'H-NMR (CDC1 3)} 6: 2.69 (3H, s), 2.76 (3H, s), 6.97 (IH, d, J = 9Hz),

7.47-7.63 (5H, m), 7.67 (2H, d, J = 9Hz), 7.80 (IH, d, J = 8Hz), 8.03 (2H, d, J = 8Hz),

8.77 (1H, s)

Example 18 (24)

2,5-dimethyl-1- (4-dimethylaminobenzoyl) _ 3 _phenylsulfonylindole (Compound 142)

Properties: yellow solid

Melting point: 89-92 ° C _{'H-NMR (CDC1 3)} δ: 2.45 (3H, s), 2.71 (3H, s), 3.09 (6H, s), 6.62 (2H, d, J = 9Hz),

6.94 (2H, s), 7.43-7.60 (5H, m), 7.93 (1H, s), 8.09 (2H, d, J = 9Hz)

Example 18 (25)

(1- (4-Dimethylaminobenzoyl) — 2 _methyl -3- 3-phenylsulfonylindole-5-yl) Ethyl acetate (Compound 143)

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ: 1.25 (3Η, t, J = 7Hz), 2.71 (3Η, s), 3.11 (6H, s),

4.14 (2H, q, J = 7Hz), 6.67 (2H, d, J = 9Hz), 7.09 (1H, d, J = 9Hz), 7.45-7.55 (3H, m),

7.58 (2H, d, J = 8Hz), 7.96-8.04 (3H, m), 8.06 (1H, s)

Example 18 (26)

5-benzoyl _ 1- (4-dimethylaminobenzoyl) _ 2-methyl-3-phenylsulfonylindole (Compound 144)

Properties: yellow oil

Ή- thigh _{(CDC1 3) δ: 2.79 (} 3H, s), 3.12 (6H, s), 6.65 (2H, d, J = 9Hz),

7.16 (1H, d, J = 8Hz), 7.46-7.65 (7H, m), 7.70 (IH, dd, J = 2Hz, J = 9Hz),

7.79 (2H, dd, J = 2Hz, J = 8Hz), 7.89 (IH, d, J = 9Hz), 7.97 (2H, d, J = 8Hz),

8.50 (lH, d, J = 2Hz)

Example 18 (27)

(1- (4-chlorobenzoyl) — 2-methyl-3-phenylsulfonylindole 1-5-yl) Benzyl acetate (Compound 145)

Properties: pale yellow solid

Melting point: 133-135 ° C

_{'H-NMR (CDC1 3)} 6: 2.75 (3H, s), 3.78 (2H, s), 5.14 (2H, s), 6.84 (1H, d, J = 8.5Hz), 7.08 (IH, d, J = 6.5Hz), 7.3-7.4 (5H, m), 7.45-7.52 (4H, m), 7.52-7.6 (IH, m),

7.66 (2H, d, J = 9Hz), 8.0 (2H, d, J = 7.5Hz), 8.11 (1H, s)

Example 18 (28) 1- (4-methylbenzene) _ 2-methyl-3-phenylsulfonyl-5-phenylsulfonylmethylindole (Compound 146)

Properties: pale red powder

Melting point: 2 26.5-2 28 ° C

_{'H-NMR (CDC1 3)} δ: 2.71 (3Η, s), 4.42 (2H, s), 6.86 (IH, d, J = 9Hz),

7.01 (IH, d, J = 9Hz), 7.44-7.70 (12H, m), 7.95 (2H, d, J = 8Hz), 7.99 (1H, s) Example 18 (2 9)

1- (4-methylbenzoyl) — 5 _cyanomethyl-2-methyl -3-phenylsulfonylindole (Compound 147)

Properties: slightly red powder

Melting point: 1 2 3.4-1 24t:

_{'H-NMR (CDC1 3)} δ: 2.75 (3Η, s), 3.85 (. 2H s), 6.93 (IH, d, J = 9Hz),

7.14 (1H, d, J = 9Hz), 7.49-7.62 (5H, m), 7.66 (2H, dd, J = 2Hz, J = 7Hz),

8.00 (2H, dd, J = 2Hz, J = 7Hz), 8.lKlH, s)

Example 18 (30)

1- (4-benzobenzene) — 2-methyl-3-phenylsulfonyl indole 5-benzyl carboxylate (Compound 1 48)

Properties: colorless powder

Melting point: 144—144.5 ° C

'H- thigh _{(CDC1 3) δ: 2.78 (} 3Η, s), 5.41 (2Η, s), 6.94 (IH, d, J = 9Hz),

7.35-7.62 (10H, m), 7.66 (2H, d, J = 9Hz), 7.87 (1H, dd, J = 2Hz, J = 9Hz),

8.02 (2H, d, J = 8Hz), 8.88 (lH, s)

Example 18 (3 1)

2- (1- (4-chlorobenzoyl) _ 2-methyl-3-phenylsulfonylindyl 5-ylmethylsulfonyl) Methyl benzoate (Compound 1 49) Properties: yellow oil

_{'H-NMR (CDC1 3)} 6 2.61 (3H, s), 4.06 (3H, s), 4.86 (2H, s), 6.82 (IH, d, J = 9Hz), 7.08 (1H, d, J = 8Hz ), 7.40 (IH, t, J = 8Hz), 7.49 (2H, d, J = 9Hz), 7.52 (2H, d, J = 9Hz), 7.57 (2H, d, J = 9Hz), 7.62 (IH, t, J = 9Hz), 7.65 (2H, d, J = 9Hz), 7.70 (IH, d, J = 8Hz), 7.99 (2H, d, J = 8Hz), 8.13 (lH, s)

Example 18 (32)

5-(benzylsulfonyl) methyl-1 _ (4 _ benzoyl) _2-methyl 3- phenylsulfonylindole (Compound 150)

Properties: yellow powder

Melting point: 208. 7—21 1

_{Ή-NMR (CDC 1 3)} δ: 2.75 (3Η, s), 4.15 (2H, s), 4.20 (2H, s), 6.96 (1H, d, J = 9Hz), 7.22 (IH, d, J = 7Hz), 7.39-7.57 (10H, m), 7.69 (2H, d, J = 9Hz), 8.02 (2H, d, J = 8Hz), 8.19 (1H, s)

Example 18 (33)

5-Benzylsulfonylmethyl-11- (4-dimethylaminobenzoyl) _2-methyl_3-phenylsulfonylindole (Compound 151)

Properties: yellow solid

Melting point: 94—96.5V

'H-NMR (CDC1 ₃ ) δ 2.74 (3H, s), 3.12 (6H, s), 4.12 (2H, s), 4.22 (2H, s),

6.65 (2H, d, J = 9Hz), 7.12 (1H, d, J = 9Hz), 7.24 (IH, d, J = 9Hz), 7.38-7.52 (8H, m),

7.59 (2H, d, J = 9Hz), 8.01 (2H, dd, J = 2Hz, J = 9Hz), 8.15 (IH, s)

Example 18 (34)

5-Benzylsulfonylmethyl-1_ (3-dimethylaminobenzoyl) -2-methyl-3-phenylsulfonylindole (Compound 152)

Properties: yellow solid

Melting point: 169—169.5 ° C _{'H-NMR (CDC1 3)} δ: 2.73 (3H, s), 2.99 (6H, s), 4.12 (2H, s), 4.21 (2H, s),

6.87 (1H, d, J = 8Hz) 7.01 (IH, d, J = 9Hz), 7.07 (IH, s), 7.11 (IH, d, J = 8Hz),

7.22 (IH, dd, J = 2Hz, J = 7Hz), 7.29 (IH, t, J = 8Hz), 7.44 (5H, brs), 7.49 (2H, t, J = 8Hz), 7.54 (IH, d, J = 7Hz), 8.01 (2H, d, J = 7Hz), 8.17 (IH, s)

Example 18 (35)

2- (1- (4-Dimethylaminobenzoyl) -1-2-methyl-3-phenylsulfonylindole 5-methylmethylsulfonyl) Methyl benzoate (Compound 153)

Properties: pale yellow solid

Melting point: 104—104.5

_{'H-NMR (CDC1 3)} δ: 2.71 (3Η, s), 3.11 (6Η, s), 4.06 (3Η, s), 4.86 (2Η, s),

6.62 (2Η, d, J = 9Hz), 6.96 (1H, d, J = 9Hz), 7.06 (1H, dd, J = lHz, J = 9Hz),

7.34 (IH, t, J = 8Hz), 7.47-7.59 (7H, m), 7.68 (IH, d, J = 8Hz),

7.95 (2H, dd, J = lHz, J = 9Hz), 8.04 (1H, s)

Example 18 (36)

1- (3-Dimethylaminobenzoyl) — 2 _methyl-3-phenylsulfonyl-1-5-phenylsulfonylmethylindole (Compound 154)

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ 2.69 (3H, s), 2.98 (6H, s), 4.42 (2H, s),

6.85 (1Η, d, J = 8Hz), 6.99 (2H, d, J = 7Hz), 7.03 (IH, s), 7.3-7.31 (IH, m),

7.42-7.52 (1H, m), 7.59-7.64 (5H, m), 7.93 (2H, d, J = 8Hz)

Example 18 (37)

2- (1- (3-Dimethylaminobenzoyl) -1-2-methyl-3-phenylsulfonylindole-1-5-methylsulfonyl) Methyl benzoate (Compound 155)

Properties: yellow solid Melting point: 95- 96 ° C

_{'Η - NMR (CDC1 3)} δ: 2.70 (3Η, s), 2.97 (6Η, s), 4.06 (3Η, s), 4.86 (2Η, s),

6.82 (IH, d, J = 8Hz), 6.94 (IH, d, J = 9Hz), 6.99 (IH, d, J = 9Hz), 7.02 (IH, s),

7.07 (IH, d, J = 10Hz), 7.27-7.29 (1H, m), 7.36 (1H, t, J = 8Hz),

7.49-7.52 (3H, m), 7.55-7.61 (2H, m), 7.69 (IH, d, J = 8Hz), 7.98 (2H, d, J = 8Hz), 8.09 (1H, s)

Example 18 (38)

1- (4-Dimethylaminobenzoyl) _ 2 _Methyl-3-phenylsulfonyl-5-phenylsulfonylmethylindole (Compound 1 56)

Properties: yellow oil

_{'H-NMR (CDC1 3)} δ 2.68 (3Η, s), 3.11 (6H, s), 4.42 (2Η, s), 6.62 (2Η, d, J = 9Hz),

6.99 (IH, d, J = 9Hz), 7.42 (2H, t, J = 8Hz), 7.48 (2H, t, J = 8Hz), 7.54-7.59 (4H, m),

7.62 (2H, d, J = 7Hz), 7.88 (2H, d, J = 9Hz), 7.91 (2H, d, J = 8Hz)

Example 18 (39)

2_methyl-1_ (3-dimethylamino-2-methylbenzoyl) _3-phenylsulfonyl-5 _phenylsulfonylmethylindole (Compound 157) Properties: pale yellow powder

Melting point: 99_101

'H-NMR (DMS0-d ₆ ) δ: 2.04 (3Η, s), 2.53 (3H, s), 2.62 (6Η, s), 4.82 (2Η, s),

6.95 (IH, d, J = 9Hz), 7.02 (IH, dd, J = 2Hz, J = 9Hz), 7.08 (IH, d, J = 7Hz),

7.30 (IH, t, J = 8Hz), 7.36 (IH, d, J = 7Hz), 7.55 (2H, t, J = 8Hz), 7.60 (2H, t, J = 8Hz), 7.68-7.74 (4H, m), 7.90 (2H, dd, J = 2Hz, J = 8Hz), 7.91 (IH, s)

Example 18 (40)

5-Benzylsulfonylmethyl-2-methyl-1- (3-dimethylamino-2-methylbenzoyl) -1-3-phenylsulfonylindole (Compound 158) Properties: pale yellow powder Melting point: 98-99 ° C

Ή-NMR (DMS0-d ₆ ) δ: 2.11 (3H, s) 58 58 (3H, s) 64 64 (6H, s), 4.44 (2H, s),

4.61 (2H, s), 7.06 (1H, d, J = 9Hz), 7.10 (1H, d, J = 7Hz), 7.20 (1H, d, J = 9Hz),

7.30 (IH, t, J = 8Hz), 7.36-7.40 (6H, in), 7.56 (2H, t, J = 8Hz), 7.64 (IH, d, J = 7Hz), 8.01 (2H, d, J = 8Hz), 8.13 (lH, s)

Example 18 (41)

5-tert e-butoxycarponylamino-1- (4-dimethylaminobenzoyl) — 2-methyl_3_ (2-pyridylsulfonyl) indole (Compound 159)

Properties: colorless powder

Melting point: 88-91

Ή-NMR (DMS0-d ₆ ) δ 1.47 (9H, s), 2.64 (3H, s), 3.07 (6H, s), 6.78 (2H, d, J = 9 Hz),

6.93 (1H, d, J = 8Hz), 7.22 (1H, brs), 7.48 (2H, d, J = 9Hz), 7.67 (IH, t, J = 8Hz), 8.10 (IH, s), 8.13-8.21 (2H, m), 8.69 (1H, d, J = 5Hz), 9.33 (1H, s)

Example 18 (42)

3- (2-Methyl-11- (3-dimethylamino-2-methylbenzoyl) —3-phenylphenylsulfonylindole-5_yl) _2,4 (1H, 3H) -quinazolindione (Compound 160)

Properties: pale yellow powder

Melting point: 159—161 ° C

Ή-NMR (DMS0-d ₆ ) δ: 2.20 (3Η, s), 2.64 (3H, s), 2.67 (6H, s), 7.11 (IH, d, J = 9 Hz), 7.17 (2H, dd, J = 2Hz, J = 8Hz), 7.24 (2H, d, J = 8Hz), 7.33 (IH, dd, J = 2Hz, J = 8Hz),

7.39 (IH, d, J = 8Hz), 7.59-7.64 (2H, m), 7.68-7.73 (2H, m), 7.95 (IH, d, J = 8Hz), 7.97-8.10 (3H, m), 11.56 (IH, s)

Example 18 (43)

3- (2-methyl-11- (4-dimethylaminobenzoyl) -3-phenylsulfur Honylindoneru 5 _yl) — 2,4 (1H, 3H) -quinazolinedione (compound 16 1)

Properties: pale yellow powder

Melting point: 202-204 ° C

'H-NMR (DMSO-d ₆ ) δ: 2.73 (3Η, s), 3.09 (6H, s), 6.82 (2H, d, J = 9Hz),

7.10 (1H, d, J = 8Hz), 7.15 (1H, d, J = 8Hz), 7.26 (2H, d, J = 8Hz), 7.56-7.64 (4H, m), 7.65-7.74 (2H, in) , 7.96 (2H, d, J = 2Hz), 8.03 (2H, d, J = 8Hz), 11.56 (1H, s) Example 18 (44)

2- (5-bromo-1- (3-dimethylamino-2-methylbenzoyl) _2-methylindole-3-ylsulfonyl) Benzyl benzoate (Compound 162) Properties: Brown oil

_{'H-NMR (CDC1 3)} δ: 2.24 (3Η, s), 2.54 (3Η, s), 2.71 (6H, s), 5.30 (2H, s),

6.91-6.99 (2H, m), 7.18-7.24 (2H, m), 7.30-7.42 (5H, m), 7.56-7.62 (3H, m), 8.05-8.10 (1H, m), 8.16 (1H, d , J = 2Hz)

Example 18 (45)

5-Bromo_1- (4-methoxybenzoyl) — 3-phenylthioindole (Compound 163)

Properties: colorless powder

Melting point: 110-113 ° C

'.Eta. Awakening: _{(CDC1 3) δ: 3.91 (} 3Η, s), 7.04 (2H, d, J = 9Hz), 7.11-7.19 (3H, m), 7.19-7.25 (2H, m), 7.50 (1H, dd, J = 9Hz, J = 2Hz), 7.65-7.69 (2H, m),

7.76 (2H, d, J = 9Hz), 8.24 (1H, d, J = 9Hz)

Example 18 (46)

5-Bromo_1- (4-methoxybenzoyl) — 3- (2-pyridylthio) indole (Compound 164)

Properties: colorless powder Melting point: 1 47 _ 1 49 ° C

'.Eta. Awakening: _{(CDC1 3) δ: 3.91 (} 3H, s), 6.88 (IH, d, J = 8Hz), 6.99-7.09 (3H, m),

7.44 (1H, dt, J = 8Hz, J = 2Hz), 7.53 (IH, dd, J = 9Hz, J = 2Hz), 7.69 (IH, d, J = 2Hz), 7.71-7.81 (3H, m), 8.27 (1H, d, J = 9Hz), 8.40 (IH, d, J = 5Hz)

Example 18 (47)

5-Bromo _ 3 _ (4_chlorophenylthio) 1-11 (4-methoxybenzoyl) indole (compound 1 65)

Properties: colorless powder

Melting point: 1 3 3 _ 1 3 5

'HNR (CDC1 ₃ ) δ 7.04 (2Η, d, J = 9 Hz), 7.07 (2H, d, J = 9 Hz), 7.19 (2H, d, J = 9 Hz),

7.51 (IH, dd, J = 9Hz, J = 2Hz), 7.63 (IH, d, J = 2Hz), 7.68 (IH, s), 7.76 (2H, d, J = 9Hz),

8.23 (lH, d, J = 9Hz)

Example 18 (48)

5-Bromo-1- (4-methoxybenzoyl) — 3 -— (4-methylphenylthio) indole (Compound 166)

Properties: colorless powder

Melting point: 1 34 _ 1 36

'H-NMR (CDC1 ₃ ) δ: 2.28 (3Η, s), 3.91 ( ₃ ), s), 6.99-7.05 (4 m, m),

7.09 (2Η, d, J = 8Hz), 7.49 (IH, dd, J = 9Hz, J = 2Hz), 7.64 (IH, s), 7.66 (1H, d, J = 2Hz), 7.75 (1H, d, J = 8Hz), 8.22 (1H, d, J = 9Hz)

Example 18 (49)

5-Bromo_1_ (4-methoxybenzoyl) — 3- (4-nitrophenylthio) indole (Compound 1667)

Properties: pale yellow powder

Melting point: 1 5 7—1 5 9 ° C

_{Ή-NMR (CDC1 3) δ} : 3.93 (3Η, s), 6.99 (2Η, d, J = 9Hz), 7.50 (1H, dd, J = 9Hz, J = 2Hz), 7.54 (IH, s), 7.60 (2H, d, J = 9Hz), 7.71 (2H, d, J = 9Hz), 7.74 (IH, d, J = 2Hz), 8.14 (lH, d, J = 9Hz) , 8.20 (2H, d, J = 9Hz)

Example 18 (50)

5_Bromo-1- (4-dimethylaminobenzoyl) _3-phenylthioindole (Compound 168)

Properties: colorless powder

Melting point: 138- 140 ° C

_{'H-NMR (CDC1 3)} δ 3.10 (6Η, s), 6.73 (2Η, d, J = 9Hz), 7.10-7.18 (3H, m),

7.20-7.24 (2H, m), 7.45-7.50 (1H, m), 7.67 (1H, d, J = 2Hz), 7.72 (2H, d, J = 9Hz), 7.77 (lH, s), 8.17 (lH , d, J-9Hz)

Example 18 (51)

5-Bromo-1 _ (3-dimethylaminobenzoyl) _3_ (2-pyridylthio) indole (Compound 169)

Properties: yellow powder

Melting point: 185-188 ° C

_{'H-NMR (CDC1 3)} δ: 3.01 (6Η, s), 6.87 (IH, d, J = 8Hz), 6.94 (IH, d, J = 8Hz),

6.98-7.03 (2H, m), 7.04 (1H, s), 7.36 (IH, t, J = 8Hz), 7.44 (IH, t, J = 8Hz),

7.54 (IH, dd, J = 9Hz, J = 2Hz), 7.68 (IH, d, J = 2Hz), 7.76 (1H, s), 8.34 (IH, d, J = 9Hz),

8.38-8.41 (1H, m)

Example 18 (52)

5-bromo-11- (3-dimethylaminobenzoyl) -3-phenylthioindole (compound 170)

Properties: yellow powder

Melting point: 151-163 ° C

_{'H-NMR (CDC1 3)} δ: 3.01 (6Η, s), 6.94 (IH, d, J = 8Hz), 6.99 (IH, d, J = 8Hz), 7.03 (IH, s), 7.11-7.19 ( 3H, m), 7.19-7.29 (2H, m), 7.36 (IH, t, J = 8Hz), 7.51 (IH, dd, J = 9Hz, J = 2Hz), 7.66 (IH, d, J = 2Hz), 7.69 (IH, s), 8.31 (IH, d, J = 9Hz) )

5-Bromo-1_ (4-chlorobenzoyl) — 2-Methyl-3_phenylthioindole (Compound 17 1)

Properties: brown powder

Melting point: 1 2 0— 1 2 2 ° C

_{'H-NMR (CDC1 3)} 6: 2.52 (3H, s), 6.95 (2Η, d, J = 9Hz), 7.08-7.16 (3H, m),

7.20-7.25 (3H, m), 7.51 (3H, d, J = 9Hz), 7.66 (IH, d, J = 2Hz), 7.69 (2H, d, J = 8Hz), 8.08 (1H, d, J = 9Hz)

Example 1 9 (1)

(1-(4-methylbenzoyl) — 2-methyl-3-phenylsulfonylindo —lu-5-yl) Acetic acid (Compound 172)

(1- (4-chlorobenzene) _2-Methyl-3-phenylsulfonyl alcohol 5-yl) Benzyl acetate 25 Omg is converted to dichlorone 1 Om1 and tetrahydrofuran 10 ml. Dissolved. Hydrogenation (room temperature, 19 hours) was performed in the presence of 50 mg of palladium hydroxide on carbon. The catalyst was filtered. The filtrate was concentrated. The residue was subjected to column chromatography (silica gel; chloroform-form methanol = 10/1) to obtain 9 Omg of the above compound.

Properties: colorless powder

Melting point: 105-106

_{'H-NMR (CDC1 3)} δ: 2.74 (3Η, s), 3.77 (2Η, s), 6.82-6.89 (IH, m), 7.02-7.09 (IH, m), 7.45-7.60 (5H, m) , 7.66 (2H, d, J = 9Hz), 8.0 (2H, d, J = 7.5Hz), 8.10 (1H, s) Example 19 (2)

The following (Compound 1773) was obtained in the same manner as in Example 19 (1).

1-(4-chlorobenzoyl) — 2-methyl-3-phenylsulfonyl indole 5- 5-carboxylic acid (compound 1 73) Properties: colorless powder

Melting point: 204—207 ° C

'H-NMR (DMSO-d ₆ ) δ: 2.69 (3Η, s), 7.02-7.12 (1H, m), 7.60-7.71 (5H, m), 7.79-7.82 (3H, m), 8.00 (2H, d, J = 8Hz), 8.62 (1H, s)

Example 20

5- (1- (4-methylbenzene) —2-methyl-3-phenylsulfonylindole-5-methyl) methyltetrazole (Compound 174)

224 mg of 11- (4-chlorobenzoyl) -15-cyanomethyl-12-methyl-3-phenylsulfonylindole and 206 mg of trimethyltin azide were added to 1 ml of toluene and refluxed for 18 hours. The solvent was concentrated, 5 ml of toluene was added, and the mixture was filtered. 3 ml of 14.6% Z-dioxane hydrochloride was added to 5 ml of toluene, and the mixture was stirred at room temperature for 21 hours. The resulting solid was filtered and washed with ether to give 15 Omg of the above compound.

Properties: colorless powder

Ή-NMR (DMS0-d ₆ ) δ: 2.65 (3Η, s), 4.37 (2Η, s), 7.07 (1H, d, J = 9 Hz),

7.32 (2H, dd, J = lHz, J = 9Hz), 7.48 (2H, d, J = 9Hz), 7.53 (2H, t, J = 8Hz),

7.59 (2H, t, J = 9Hz), 7.76 (1H, s), 7.89 (2H, dd, J = lHz, J = 9Hz), 12.22 (1H, brs) Example 21 (1)

5-Benzylamino-11- (4-dimethylaminobenzoyl) -3-phenylsulfonylindole (Compound 175)

5-benzoylamino-3-phenylsulfonylindole 12 Omg solution in tetrahydrofuran 5 ml 1 ml of diisopropylethylamine 0.5 ml, 4-dimethylaminoaminobenzoyl chloride 20 Omg and 4-dimethylaminopyridine 2 mg Stirred at room temperature for 18 hours. The solvent was distilled off under reduced pressure. To the residue was added 3 Oml of chloroform, and the mixture was washed with 6 Om1X2 of saturated aqueous sodium hydrogen carbonate. After drying, it was concentrated. The residue was subjected to column chromatography (silica gel; = 20Z1). Ether was added and filtered to obtain 8 Omg of the above compound. Properties: light brown powder

Melting point: 217-218 ° C

Ή-NMR (DMS0-d ₆ ) δ 3.09 (6Η, s), 6.88 (2H, d, J = 9 Hz), 7.56-7.64 (5H, m),

7.67 (IH, d, J = 7Hz), 7.71 (2H, d, J = 8Hz), 7.88 (IH, d, J = 7Hz), 8.00-8.05 (3H, m),

8.08 (2H, d, J = 8Hz), 8.21 (IH, s), 8.41 (1H, s), 10.46 (1H, s)

Example 21 (2) _ (61)

The following (Compound 176) — (Compound 235) were obtained in the same manner as in Example 21 (1).

Example 21 (2)

5-Acetylamino _ 1 _ (4-Benzoyl) —3-Phenylsulfonyl indole (Compound 176)

Properties: colorless powder

Melting point: 199.5—202

'H-NMR (DMS0-d ₆ ) <5: 2.09 (3H, s), 7.61-7.71 (4H, m), 7.74 (2Η, d, J = 8Hz),

7.89 (2H, d, J = 8Hz), 8.03 (IH, d, J = 8Hz), 8.05 (2H, d, J = 9Hz), 8.17 (IH, d, J = 9Hz),

8.23 (1H, s), 10.17 (1H, s)

Example 21 (3)

N— (1— (4-Dimethylaminobenzoyl) — 3-phenylsulfonylindole—5-yl) — N ′ —phenylperylene (compound 177)

Properties: light brown powder

Melting point: 232.5-233.5 ° C

'H-NMR (DMS0-d ₆ ) δ: 3.09 (6Η, s), 6.88 (2Η, d, J = 9Hz), 6.99 (IH, t, J = 8Hz), 7.30 (2H, t, J = 8Hz) ), 7.42 (IH.dd, J = 2Hz, J = 9Hz), 7.49 (2H, d, J = 8Hz),

7.62 (2H, t, J = 7Hz), 7.67 (IH, d, J = 7Hz), 7.70 (2H, d, J = 9Hz), 7.98 (IH, d, J = 9Hz),

8.04 (2H, dd, J = 2Hz, J = 7Hz), 8.10 (IH, d, J = 2Hz), 8.17 (IH, s), 8.65 (1H, s), 8.92 (lH, s)

Example 2 1 (4)

1- (3-Dimethylamino-2-methylbenzoyl) -5- (4-toluenesulfonylamino) -1-3-phenylsulfonylindole (compound 178)

Properties: colorless powder

Melting point: 69.5-70.5

Ή-NMR (DMS0-d ₆ ) δ 2.17 (3Η, s), 2.30 (3H, s), 2.69 (6Η, s), 7.19-7.26 (2Η, s), 7.28 (2Η, d, J = 8Hz) , 7.33-7.38 (2H, m), 7.54-7.64 (5H, m), 7.71 (1H, s),

7.72-7.77 (IH, m), 7.93 (2H, d, J = 8Hz), 8.08 (IH, d, J = 9Hz), 10.46 (IH, s) Example 2 1 (5)

3- (1— (4-Dimethylaminobenzoyl) —3-Phenylsulfonylindo—Lu5_yl) 1,2,4 (1H, 3H) -quinazolinedione (Compound 179) Properties: colorless powder

Melting point: 180—182 ° C

'Η-NMR (DMS0-d ₆ ) δ: 3.10 (6Η, s), 6.89 (2Η, d, J = 9Hz), 7.25 (2H, d, J = 9Hz), 7.38 (IH, d, J = 9Hz) ), 7.58 (2H, t, J = 8Hz), 7.65-7.75 (4H, m), 7.88 (IH, s),

7.96 (IH, d, J = 8Hz), 8.07-8.11 (3H, m), 8.3 (IH, s), 11.57 (1H, s)

Example 2 1 (6)

5-tert-butoxycarbonylamino_1- (4-dimethylaminobenzoyl) -1-3-phenylsulfonylindole (Compound 180)

Properties: colorless powder

Melting point: 166—168 ° C

Ή-NMR (DMS0-d ₆ ) δ 1.50 (9H, s), 3.08 (6H, s), 6.87 (2H, d, J = 9Hz),

7.53 (lH, d, J = 9Hz), 7.59-7.62 (2H, m), 7.66-7.69 (3H, m), 7.94 (IH, d, J = 9Hz),

8.02 (3H, d, J = 8Hz), 8.14 (IH, s), 9.52 (IH, brs)

Example 2 1 (7) 5-Bromo-3-formyl-1- (4-methoxybenzoyl) indole (Compound 181)

Properties: yellow powder

Melting point: 169—17 1 ° C

_{'H-NMR (CDC1 3)} δ: 3.94 (3Η, s), 7.08 (2Η, d, J = 9Hz), 7.56 (IH, d, J = 9Hz), 7.79 (2H, d, J = 9Hz), 8.01 (IH, s), 8.12 (IH, d, J = 9Hz), 8.51 (IH, s), 10.05 (IH, s) Example 2 1 (8)

5-Bromo-1 _ (4-chlorobenzoyl) _ 3 _Formylindole (Compound 182)

Properties: colorless powder

Melting point: 16 1- 164 ° C

'Η-Oki (CDC ") δ 7.53-7.62 (3Η, m), 7.74 (2Η, d, J = 9Hz), 7.92 (IH, s), 8.18 (IH, d, J = 9Hz), 8.50 (1H , D, J = 9Hz), 10.04 (IH, s)

Example 2 1 (9)

1 Benzoyl-3-formyl-5-methoxyindole (Compound 183) Properties: colorless powder

Melting point: 127-128 ° C

_{'H-NMR (CDC1 3)} δ 3.92 (IH, s), 7.08 (IH, d, J = 9Hz), 7.50-7.63 (2H, m), 7.63-7.71 (IH, m), 7.71-7.88 (3H , m), 7.90 (IH, s), 8.22 (IH, d, J = 9Hz),

10.03 (1H, s)

Example 2 1 (10)

3_formyl_ 1 _ (412-trobenzyl) indole (compound 184) Properties: brown powder

Melting point: 209—2 1 1 ° C

_{'H-NMR (CDC1 3)} δ 7.43-7.57 (2Η, m), 7.82 (IH, s), 7.97 (2H, d, J = 9Hz), 8.29-8.38 (2H, m), 8.47 (2H, d , J = 9Hz), 10.08 (1H, s) Example 2 1 (1 1)

3-formyl-1-1 (2-toindole (compound 185)

Properties: colorless powder

Melting point: 128-1 30 ° C

_{'H-NMR (CDC1 3)} δ: 7.41-7.55 (3Η, m), 7.55-7.67 (IH, m), 7.73-7.85 (2H, m), 7.85-7.95 (IH, m), 8.28-8.42 ( 2H, m), 10.03 (IH, s)

Example 2 1 (12)

1- (4-Benzoyl) _ 3 _Formylindole (Compound 186) Properties: colorless powder

Melting point: 1 32— 1 34

_{'H-NMR (CDC1 3)} δ: 7.41-7.55 (2Η, m), 7.61 (2H, d, J = l 1Hz), 7.77 (2H, d, J = l 1Hz),

7.91 (IH, s), 8.23-8.41 (2H, m), 10.10 (1H, s)

Example 2 1 (13)

1- (2,6-dicyclobenzoyl) — 3-formylindole (compound 187)

Melting point: 1 59— 16 1:

_{'H-NMR (CDC1 3)} δ: 7.40-7.60 (6Η, m), 8.32 (IH, d, J = 7Hz), 8.65 (IH, d, J = 7Hz), 10.03 (1H, s)

Example 2 1 (14)

5-Bromo _ 3-formyl- 1- (412-trobenzyl) indole (Compound 188)

Properties: pale yellow powder

Melting point: 236— 238 ° C (dec.)

'Eta -丽_{R (CDC1 3) δ 7.63 (} IH, d, J = 8Hz), 7.82 (IH, s), 7.98 (2H, d, J = 7Hz),

8.25 (IH, d, J = 8Hz), 8.48 (2H, d, J = 7Hz), 8.51 (1H, s), 10.04 (IH, s) Example 2 1 (1 5)

5-Bromo_3-formyl-1_ (4-methyl-1,2,3-thiadiazole-5-capillonyl) indole (Compound 189)

Properties: pale yellow powder

Melting point: 189-190 ° C

_{'H-NMR (CDC1 3)} δ: 2.88 (3Η, s), 7.63 (IH, d, J = 8Hz), 7.73 (IH, s),

8.29 (IH, d, J = 8Hz), 8.51 (IH, s), 10.05 (1H, s)

Example 2 1 (1 6)

5-Bromo-3-formyl-1- (4_trifluoromethylbenzoyl) indole (Compound 190)

Properties: pale yellow powder

Melting point: 165_ 166

_{'H-NMR (CDC1 3)} δ: 7.61 (IH, dd, J = 9Hz, J = 2Hz), 7.86 (IH, s), 7.90 (4H, s), 8.25 (IH, d, J = 9Hz), 8.51 (1H, d, J = 2Hz), 10.04 (IH, s)

Example 2 1 (17)

5-Bromo_3-formyl-11- (1-naphthoyl) indole (compound 19 1)

Properties: pale yellow powder

Melting point: 149 _ 1 5 1

_{Ή-NMR (CDC1 3) 6} : 7.52-7.70 (5H, m), 7.70-7.80 (IH, m), 7.89 (IH, d, J = 8Hz), 8.01 (IH, d, J = 8Hz), 8.14 (1H, d, J = 8Hz), 8.37 (1H, d, J = 8Hz), 8.51 (IH, s), 9.89 (1H, s)

Example 2 1 (18)

5-Promo 3-Formyl-1_ (2-furoyl) indole (Compound 192) Properties: colorless powder

Melting point: 1 35— 1 37 ° C _{'H-NMR (CDC1 3)} 6: 6.75 (1H, s), 7.50-7.62 (2H, m), 7.80 (1H, s), 8.33 (1H, d, J = 9Hz), 8.51 (1H, s) , 8.75 (1H, s), 10.15 (1H, s)

Example 2 1 (1 9)

5_bromo_1- (4-biphenylcarbonyl) -3-formylindole (compound 193)

Properties: colorless powder

Melting point: 1 79— 18 1 ° C

_{'H-NMR (CDC1 3)} δ: 7.40-7.61 (4Η, m), 7.61-7.72 (2Η, m), 7.72-7.90 (4Η, m), 8.04 (1Η, s), 8.23 (1Η, d, J = 9Hz), 8.52 (IH, s), 10.06 (1Η, s)

Example 2 1 (20)

5-Bromo-3-formyl_1- (4- (1-pyrrolyl) benzoyl) indole (Compound 194)

Melting point: 20 1— 203 X

_{'H-NMR (CDC1 3)} δ: 6.45 (2Η, s), 7.22 (2Η, s), 7.56-7.77 (3Η, m),

7.89 (2Η, d, J = 8Hz), 8.02 (IH, s), 8.18 (IH, d, J = 9Hz), 8.52 (1H, s), 10.07 (IH, s) Example 2 1 (2 1)

5-bromo-3-formyl-1- (3,4,5-trimethoxybenzoyl) indole (Compound 195)

Properties: pale yellow powder

Melting point: 189-192 ° C

_{'H-NMR (CDC1 3)} δ: 3.91 (6H, s), 3.98 (3H, s), 6.99 (2H, s), 7.59 (1H, d, J = 9Hz),

8.03 (1H, s), 8.14 (1H, d, J = 9Hz), 8.51 (IH, s), 10.06 (IH, s)

Example 2 1 (22)

5-Bromo_3-formyl-1- (4-formylbenzyl) India (Compound 196)

Properties: brown powder Melting point: 210-212 ° C

_{'H-NMR (CDC1 3)} δ: 7.62 (IH, d, J = 9Hz), 7.86 (IH, s), 7.95 (2H, d, J = 8Hz),

8.13 (2H, d, J = 8Hz), 8.24 (IH, d, J = 9Hz), 8.52 (IH, s), 10.04 (IH, s), 10.19 (1H, s) Example 2 1 (2 3)

4- (5-Bromo-3-formylindole-1-yl) methyl carbonylbenzoate (Compound 197)

Properties: yellow powder

Melting point: 1 95—1 9 7 ° C

_{'H-NMR (CDC1 3)} δ: 4.01 (3Η, s), 7.60 (IH, d, J = 9Hz), 7.80-7.91 (3H, m),

8.19-8.33 (3H, m), 8.51 (1H, s), 10.03 (1H, s)

Example 2 1 (24)

4- (5-Promo 3-formylindole-11-yl) carbonylbenzoic acid (Compound 198)

Properties: colorless powder

Melting point:> 2 90

'H-NMR (DMSO-d ₆ ) δ: 7.70 (IH, d, J = 9 Hz), 7.98 (2Η, d, J = 8 Hz), 8.16 (2H, d, J = 8 Hz), 8.28 (IH, d , J = 9Hz), 8.32 (1H, s), 8.54 (IH, s), 10.02 (IH, s)

Example 2 1 (2 5)

3-formyl-1_ (4-methoxybenzoyl) -5-nitroindole (Compound 199)

Properties: yellow powder

Melting point: 247—250 ° C

'H-NMR (DMS0-d ₆ ) δ: 3.91 (3Η, s), 7.21 (2Η, d, J = 8 Hz), 7.91 (2H, d, J = 9 Hz), 8.37 (2H, s), 8.80 ( IH, s), 8.98 (1H, s), 10.11 (1H, s)

Example 2 1 (2 6)

4-Bromo-3-formyl-1- (4-methoxybenzoyl) indole (Compound (2 0 0)

Properties: brown powder

Melting point: 1 7 2— 1 74:

_{'H-NMR (CDC1 3)} δ 3.93 (3Η, s), 7.05 (2Η, d, J = 9Hz), 7.30 (IH, t, J = 8Hz), 7.62 (IH, d, J-8Hz), 7.76 (2H, d, J = 9Hz), 8.18 (1H, s), 8.34 (IH, d, J = 8Hz), 11.00 (1H, s)

Example 2 1 (2 7)

5-bromo-1- (4-bromobenzoyl) _ 3 _formylindole (Compound 201)

Properties: colorless powder

Melting point: 1 87-190 ° C

_{'H-NMR (CDC1 3)} δ 7.58 (IH, dd, J = 9Hz, J = 2Hz), 7.63 (2H, d, J = 9Hz),

7.73 (2H, d, J = 9Hz), 7.90 (1H, s), 8.17 (1H, d, J = 9Hz), 8.49 (IH, d, J = 2Hz),

10.03C1H, s)

Example 2 1 (2 8)

5-bromo-3-formyl-1- (4-methylbenzoyl) indole (compound 202)

Properties: colorless powder

Melting point: 15 2—15 3 ° C

_{'H-NMR (CDC1 3)} δ: 2.50 (3Η, s), 7.40 (2Η, d, J = 8Hz), 7.57 (IH, dd, J = 9Hz, J = 2Hz), 7.69 (2H, d, J = 8Hz), 7.98 (IH, s), 8.17 (IH, d, J = 9Hz), 8.49 (1H, d, J = 2Hz),

10.03 (1H, s)

Example 2 1 (2 9)

5-Bromo _ 1 _ (4-fluorobenzoyl) — 3-formylindole (Compound 203)

Properties: colorless powder Melting point: 175—176 ° C

_{'H-NMR (CDC1 3)} δ: 7.21-7.32 (2H, m), 7.58 (IH, dd, J = 9Hz, J = 2Hz),

7.79-7.88 (2H, m), 7.94 (1H, s), 8.16 (IH, d, J = 9Hz), 8.50 (IH, d, J = 2Hz),

10.04 (1H, s)

Example 21 (30)

5-bromo-1- (6-nitronicotinol) -3-formylindole (Compound 204)

Properties: pale yellow powder

Melting point: 180-182 ° C

'Eta - Awakening: _{(CDC1 3) δ: 7.55-7.64 (} 2Η, m), 7.88 (IH, s), 8.09 (IH, dd, J = 7Hz, J = 2Hz),

8.22 (1H, d, J = 9Hz), 8.51 (IH, d, J = 2Hz), 8.81 (IH, d, J = 2Hz), 10.06 (IH, s) Example 21 (31)

6-Bromo-3-formyl_1- (4-methoxybenzoyl) indole (Compound 205)

Properties: colorless powder

Melting point: 103 _ 105

_{'H-NMR (CDC1 3)} δ: 3.94 (3H, s), 7.07 (2H, d, J = 9Hz), 7.56 (IH, dd, J = 8Hz, J = 2Hz), 7.78 (2H, d, J = 9Hz), 7.98 (IH, s), 8.19 (1H, d, J = 8Hz), 8.48 (1H, d, J = 2Hz), 10.05 (1H, s)

Example 21 (32)

3-Acetyl— 1— (4_benzophenazole) Indole (Compound 206) Properties: colorless powder

Melting point: 197—199 ° C

_{'H-NMR (CDC1 3)} δ: 2.52 (3Η, s), 7.40-7.50 (2H, m), 7.59 (2H, d, J = 8Hz),

7.74 (2H, d, J = 8Hz), 7.90 (IH, s), 8.15-8.24 (IH, m), 8.33-8.44 (IH, m)

Example 21 (33) 3-Acetyl-1-1 (4-methoxybenzoyl) indole (Compound 207) Properties: colorless powder

Melting point: 1 65-1 67 ° C

_{'H-NMR (CDC1 3)} δ: 2.53 (3Η, s), 3.94 (3H, s), 7.07 (2H, d, J = 8Hz),

7.39-7.50 (2H, m), 7.79 (2H, d, J = 8Hz), 8.01 (IH, s), 8.11-8.22 (IH, m),

8.35-8.45 (IH, m)

Example 2 1 (34)

3 _acetyl- 1 _ (2-furoyl) indole (compound 208)

Melting point: 1 3 1— 1 3 3

_{'H-NMR (CDC1 3)} δ: 2.63 (3Η, s), 6.73 (IH, s), 7.39-7.48 (2H, m),

7.55 (IH, d, J = 4Hz), 7.79 (1H, s), 8.33-8.46 (2H, m), 8.67 (1H, s)

Example 2 1 (3 5)

1- (4-methoxybenzoyl) -methyl 3-indolecarboxylate (Compound 209)

Properties: colorless powder

Melting point: 146-148

_{Έ- NMR (CDC1 3) δ 3.93} (3Η, s), 7.05 (2H, d, J = 9Hz), 7.38-7.47 (2H, m), 7.77 (2H, d, J = 9Hz), 8.06 (1H, s), 8.18-8.25 (IH, m), 8.25-8.36 (1H, m) Example 2 1 (3 6)

3 _cyano-1- (4-methoxybenzoyl) indole (compound 210) Properties: colorless powder

Melting point: 1 7 9— 18 1 ° C

_{'H-NMR (CDC1 3)} δ: 3.94 (3Η, s), 7.06 (2Η, d, J = 9Hz), 7.41-7.54 (2H, m), 7.70-7.82 (3H, m), 7.92 (1H, s), 8.25-8.33 (1H, m)

Example 2 1 (3 7)

5-bromo-11- (4-methoxybenzoyl) -1-3-pentafluoropropione Ruindole (Compound 21 1)

Properties: colorless powder

Melting point: 1 13 _ 1 15:

_{'H-NMR (CDC1 3)} δ: 3.95 (3Η, s), 7.08 (2Η, d, J = 9Hz), 7.59 (IH, dd, J = 9Hz, J = 2Hz), 7.78 (2H, d, J = 9Hz), 8.07 (IH, d, J = 9Hz), 8.26 (IH, s), 8.60 (1H, d, J = 2Hz) Example 21 (38)

5-bromo-1- (4-methoxybenzoyl) _3-trifluoroacetylindole (Compound 212)

Properties: colorless powder

Melting point: 1 10— 1 12 ° C

_{Ή-NMR (CDC1 3) δ} : 3.95 (3Η, s), 7.08 (2H, d, J = 9Hz), 7.59 (1H, dd, J = 9Hz, J = 2Hz), 7.79 (2H, d, J = 9 Hz), 8.06 (IH, d, J = 9 Hz), 8.21 (1H, d, J = 2 Hz), 8.57 (IH, d, J = 2 Hz) Example 21 (39)

1- (5-bromo-11- (4-methoxybenzoyl) -3-indolyl) -2- (4-methyl-1-piperazinyl) ethanedione (Compound 213)

Properties: light brown powder

Melting point: 163_165

lH-NMR (CDCl ₃ ) δ: 2.33 (3Η, s), 2.37-2.50 (4Η, m), 3.42-3.59 (2Η, m),

3.68-3.78 (2Η, m), 3.93 (3Η, s), 7.06 (2Η, d, J = 9Hz), 7.55 (IH, d, J = 9Hz),

7.78 (2H, d, J = 9Hz), 8.08 (1H, d, J = 9Hz), 8.19 (1H, s), 8.57 (IH, s)

Example 21 (40)

5-(3-Hydroxy-3-methyl-1-butynyl) — 1- (4-methoxybenzyl) -1-3-indolecarbaldehyde (Compound 214)

Properties: colorless powder

Melting point: 150-153

'H-NMR (CDCL) δ: 1.65 (6Η, s), 2.09 (IH, s), 3.94 (3H, s), 7.07 (2H, d, J = 9Hz), 86

() I zmm

(ΖΗ6 = 1 'ΡΉΟ ^ Γδ

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(S T z Λ (-

, 0 d ^ ^: ^ d —8— (Λ (A ^^ ^-) 1 d — S

(i) τ z w

(s' Hl) 90 "0l '(s' HI) I 8

'(ZH6 = 1' P 'HI) SI8' (s' HI) Z08 '(= ί' Ρ 'ΗΖ) 6Α · ί' (ί = ί 'ΡΡ' ΗΙ) 6

06S.0 / 00df / X3d / ΐθ OAV 5-Bromo-11- (4-dimethylaminobenzoyl) — 3-phenylsulfonyl indole (Compound 2 18)

Properties: pale yellow powder

Melting point: 2 15-2 17 ° C

_{'H-NMR (CDC1 3)} δ 3.14 (6Η, s), 6.74 (2Η, d, J = 9Hz), 7.46-7.55 (3H, m), 7.55-7.60 (IH, m), 7.70 (2H, d , J = 9Hz), 7.98-8.08 (4H, m), 8.15 (1H, s) Example 2 1 (45)

5-bromo-11- (2-dimethylaminobenzoyl) — 3-phenylsulfonyl indole (Compound 2 19)

Properties: brown amorphous

_{'H-NMR (CDC1 3)} δ: 2.66 (6Η, s), 7.01-7.09 (2Η, m), 7.45-7.60 (6H, m),

7.75 (IH, s), 7.97-8.00 (2H, m), 8.04 (IH, d, J = 2Hz), 8.30 (IH, d, J = 9Hz) Example 2 1 (46)

5-Bromo-1 _ (3-dimethylaminobenzoyl) —3-phenylsulfonyl indole (Compound 220)

Properties: yellow powder

Melting point: 2 2 1—2 2 3

_{'HN R (CDC1 3) δ} : 3.03 (6Η, s), 6.93-7.00 (3H, m), 7.38-7.41 (IH, m),

7.49-7.58 (3H, m), 7.58-7.60 (1H, m), 7.96-8.01 (2H, m), 8.07 (IH, d, J = 2Hz), 8.1K1H, s), 8.22 (1H, d, (J = 9Hz)

Example 2 1 (47)

5-bromo-1- (3-dimethylamino-2-methylbenzoyl) -1-phenylsulfonylindole (compound 22 1)

Properties: brown powder

Melting point: 1 54—1 5 7

_{'H-NMR (CDC1 3)} δ 2.24 (3Η, s), 2.77 (6Η, s), 7.03 (IH, d, J = 6Hz), 7.22-7.32 (2H, m), 7.48-7.61 (4H, m), 7.96-8.05 (3H, m), 8.25 (IH, d, J = 9Hz) Example 21 (48)

3- (benzothiazole_2-ylsulfonyl) -1-5-bromo-1- (4-dimethylaminobenzoyl) indole (compound 222)

Properties: yellow powder

Melting point: 263-266 ° C

_{'H-NMR (CDC1 3)} δ 3.14 (6Η, s), 6.75 (2Η, d, J = 9Hz), 7.50-7.60 (3H, m),

7.71 (2H, d, J = 9Hz), 7.97 (IH, d, J = 9Hz), 8.05 (IH, d, J = 9Hz), 8.16 (IH, d, J = 9Hz),

8.30 (1H, d, J = 2Hz), 8.34 (lH, s)

Example 21 (49)

5_Bromo— 1— (4-Dimethylaminobenzoyl) —3— (1—Feniltetorazol-5-ylsulfonyl) indole (Compound 223)

Properties: brown powder

Melting point: 225—228

_{'H-NMR (CDC1 3)} δ 3.14 (6Η, s), 6.73 (2Η, d, J = 9Hz), 7.54 (IH, d, J-9Hz), 7.58-7.60 (4H, m), 7.60-7.66 (IH, m), 7.68 (2H, d, J = 9Hz), 7.85 (IH, s),

8.02 (1H, d, J = 9Hz), 8.08 (lH, s)

Example 21 (50)

5-Bromo-1- (4-methoxybenzoyl) _3-phenylsulfinylindole (Compound 224)

Properties: colorless powder

Melting point: 1 10— 1 12 ° C

_{'H-NMR (CDC1 3)} 6: 3.93 (3H, s), 7.06 (2Η, d, J = 9Hz), 7.45-7.55 (4H, m),

7.58 (IH, d, J = 2 Hz), 7.72 (IH, d, J = 7 Hz), 7.76 (2H, d, J = 9 Hz), 7.87 (1H, s),

8.14 (lH, d, J = 9Hz)

Example 21 (51) 1- (4-methoxybenzoyl) -1-3- (4-methylphenylsulfonyl) _5-1 (phenylethynyl) indole (compound 225)

Properties: brown powder

Melting point: 99-102 ° C

_{'H-NMR (CDC1 3)} 6: 2.40 (3H, s), 3.95 (3Η, s), 7.07 (2H, d, J = 9Hz),

7.32 (2H, d, J = 9Hz), 7.36-7.42 (3H, m), 7.57-7.61 (3H, m), 7.77 (2H, d, J = 9Hz), 7.92 (2H, d, J = 9Hz) , 8.08-8.11 (2H, m), 8.22 (1H, d, J = 9Hz)

Example 2 1 (52)

5 _benzyloxy-11- (4-methoxybenzoyl) -3- (4-methylphenylsulfonyl) indole (Compound 226)

Properties: colorless powder

Melting point: 143-145

_{'H-NMR (CDC1 3)} δ: 2.38 (3H, s), 3.94 (3H, s), 5.16 (2H, s),

7.05 (2Η, d, J = 9Hz), 7.10 (IH, dd, J = 9Hz, J = 3Hz), 7.23 (2H, d, J = 8Hz),

7.33-7.44 (4H, m), 7.48 (2H, d, J = 8Hz), 7.74 (2H, d, J = 9Hz), 7.80 (2H, d, J = 9Hz), 7.99 (lH, s), 8.16 (lH, d, J = 9Hz)

Example 2 1 (53)

5-benzyloxy 1 _ (4-dimethylaminobenzoyl) -3- (4-methylphenylsulfonyl) indole (compound 227)

Properties: colorless powder

Melting point: 164 _ 166

_{'H-NMR (CDC1 3)} δ: 3.12 (6Η, s), 5.17 (2Η, s), 6.74 (2Η, d, J = 9Hz),

7.09 (IH, dd, J = 9Hz, J = 2Hz), 7.33-7.54 (9H, m), 7.70 (2H, d, J = 9Hz),

7.89-7.92 (2H, m), 8.06-8.10 (2H, m)

Example 2 1 (54)

5-Promo-3-formyl-1-tert-butylcarboxylate tert-butyl (compound (Object 228)

Properties: colorless powder

Melting point: 167—169 ° C

_{'H-NMR (CDC1 3)} δ: 1.71 (9Η, s), 7.51 (IH, dd, J = 9Hz, J = 2Hz), 8.03 (1H, d, J = 9Hz), 8.21 (IH, s), 8.46 (IH, d, J = 2Hz), 10.07 (1H, s)

Example 2 1 (55)

4-bromo-3-formyl-1-indolecarboxylate tert-butyl (Compound 229)

Properties: colorless powder

Melting point: 120-122

_{'H-NMR (CDC1 3)} δ: 1.68 (9Η, s), 7.21-7.28 (IH, m), 7.56 (IH, d, J = 8Hz),

8.28 (IH, d, J = 8Hz), 8.39 (IH, s), 10.98 (1H, s)

Example 2 1 (56)

6_Bromo-3-formyl-1_indolecarboxylic acid tert-butyl (Compound 230)

Properties: brown powder

Melting point: 2 1 1— 2 1 3

_{'H-NMR (CDC1 3)} δ: 1.71 (9Η, s), 7.49 (IH, dd, J = 9Hz, J = 2Hz), 8.15 (IH, d, J = 9Hz), 8.19 (lH, s), 8.37 (lH, s), 10.08 (1H, s)

Example 2 1 (57)

5-tert-butyl 5-bromo-3-phenyl-1-indolecarbonate (Compound 231)

Properties: colorless powder

Melting point: 139-1411

_{'H-NMR (CDC1 3)} δ: 1.68 (9Η, s), 7.10-7.19 (3H, m), 7.19-7.24 (2H, m),

7.45 (IH, dd, J = 9Hz, J = 2Hz), 7.63 (IH, d, J = 2Hz), 7.86 (IH, s), 8.02-8.09 (IH, m) Example 2 1 (58)

5-bromo-2-methyl-3-phenylthio-1-indolecarboxylate tert-butyl (Compound 232)

Properties: colorless powder

Melting point: 1 33— 137 ° C

_{'H-NMR (CDC1 3)} δ: 1.70 (9Η, s), 2.74 (3Η, s), 7.04 (2Η, d, J = 7Hz),

7.09 (IH, t, J = 7Hz), 7.19 (2H, t, J = 7Hz), 7.37 (IH, dd, J = 9Hz, J = 2Hz),

7.63 (1H, d, J-2Hz), 8.02 (1H, d, J = 9Hz)

Example 2 1 (59)

5-Bromo_3- (2-pyridylthio) -tert-butyl indolecarboxylate (Compound 233)

Properties: colorless powder

Melting point: 127-128

_{'H-NMR (CDC1 3)} δ: 1.68 (9Η, s), 6.87 (IH, d, J = 8Hz), 6.98-7.03 (IH, m),

7.40-7.50 (2H, m), 7.65 (1H, s), 7.93 (IH, s), 8.08-8.12 (1H, m), 8.42 (1H, s) Example 2 1 (60)

5-bromo-2-methyl-3- (2-pyridylthio) -tert-butyl 1-indolecarboxylate (Compound 234)

Properties: light brown powder

_{'H-NMR (CDC1 3)} δ: 1.71 (9Η, s), 2.74 (3Η, s), 6.69 (IH, d, J = 9Hz),

6.98 (IH, dd, J = 6Hz, J = 5Hz), 7.36-7.41 (2H, m), 7.63 (IH, d, J = 2Hz),

8.04 (IH, d, J = 9Hz), 8.41 (IH, d, J = 5Hz)

Example 2 1 (6 1)

2- (5-bromo-11-tert-butoxycarbonyl-2-methylindole-13-ylthio) benzyl benzoate (Compound 235)

Properties: yellow oil 'H-NMR (CDC1 ₃ ) δ 1.71 (9H, s), 2.71 (3H, s), 5.45 (2H, s),

6.68 (IH, d, J = 8Hz), 7.09-7.12 (1H, m), 7.16-7.20 (1H, m), 7.30-7.43 (4H, m),

7.50-7.52 (2H, m), 7.57 (IH, d, J = 2Hz), 8.04 (IH, d, J = 9Hz), 8.10 (1H, d, J = 8Hz) Example 22 (1)

5— (3-chlorophenyl) —3_formyl—1— (4-methoxybenzoyl) indole (Compound 236)

5—Promote 3 _Formyl— 1— (4-Methoxybenzoyl) indole

0. lg, (3 _ Black port phenyl) dihydroxy Polan 6 6 mg, carbonate sodium 45 mg, bis triphenyl phosphine palladium chloride _{_{(PdC 1 2 (PPh 3)}} 2) 20mg, toluene 4m 1 the triphenyl phosphine 14 mg, water 1 m 1 and refluxed for 3 hours. The reaction solution was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to column chromatography (silica gel; black form) to obtain 46 mg of the above compound.

Properties: colorless powder

Melting point: 1 76 _ 1 78 ° C

• H-NMRCCDClj) δ: 3.95 (3Η, s), 7.09 (2Η, d, J = 9Hz), 7.30-7.43 (2H, m),

7.55-7.61 (1H, m), 7.61-7.71 (2H, m), 7.82 (2H, d, J = 9Hz), 8.06 (IH, s),

8.29 (1H, d, J = 9Hz), 8.54 (IH, s), 10.11 (1H, s)

Example 22 (2) One (2 1)

The following (Compound 237) — (Compound 256) was obtained in the same manner as in Example 22 (1).

Example 22 (2)

1- (4-chlorobenzene) — 3-formyl-5-phenylindole (Compound 237)

Properties: colorless powder 001

'(ui' HZ) · ί '(ΖΗ8 = ί'} Ήϊ) OS 'ί' (， = ί 'Ρ Ήΐ) I''(ΖΗ8 = ί' Ρ Ήϊ) SS 'L' (ΖΗ6 = 1 'Ρ Ή2) 'L' (s ¾) U '2' (s 29) 29 '(s' Η6) 1-1: 9 ( ² Ι3α3) Ν-Η, as τ s-^ 12:

(0

-τ-ΊΓ ^^ ΙΓΨ- £-(= ェ Ot {Λ (^^^ Λ (Λ (^ ~; -i 3-Ν)-Ζ)-

(s Ή1) 60 · 0Ι '(s ΉΙ) 8ε · 8' (ΖΗ6 = Γ 'Ρ' ΗΙ) U · 8 '(= i' Ρ Ήΐ) QZ · 8 '(s ΉΙ) 60 · 8' (ΖΗ6 = 1 'Ρ' ΗΖ) S8 'ί' Ή8) 89 'il Ί' (ω Ήΐ) \ -08 · ί '(ΖΗ6 = ί' Ρ ¾) 01 '(S ΉΟ S6 -S' (s Ήϊ) 09 : Q ( ^S I3 () Ν-Η, as 0 S-002: WW

(6 £ z

ε-("、く ^ ^ H)-Τ-(二乙 Λ (^^^ Λ (Λ (-^-3-Ν)-Ζ)-9

() Ζ z

(s' Hi-01 '(s'HI) 60'0I'(s'HI)S9'8'(ZH6 = i' P 'HI) ZS' 8 '(s' HI) 80 ί '' HZ) 66 'ί' (ΖΗ6 = ί 'ΈΖ) 88 ) 60 Ί '(S Ή2)%: 9 ( ^ε Ι3α3) Ν-Η,

(8 ε ζ ^ ir-HO- Mr .Α ^ Φ4 ^-)-I-(Nie Otmi —)--^ (^ Λ (^-£

(ε) z zm

(s Ήΐ) U · 0Ι '(s' HI) iS · 8 '(ZH6 = f' Ρ 'HI) K · 8' (s 'ΗΙ) 96' ί '(ω' Η3) 08 'i— 99' ί '("ΐ ΉΖ) 99 -L-Ζζ ui (ui ΉΖ)' Ζ-Η '(ω Ήΐ) ί'ί''ί ~ ίΖ Ί' 9 ( ^ε Ι3α3) Μ-Η, a Τ 6 ΐ -68 Τ: W

06S.0 / 00df / X3d ΪΖ9 / ΐθ OAV 7.78 (2H, d, J = 9Hz), 8.07 (IH, s), 8.22 (IH, d, J = 8Hz), 8.47 (1H, d, J = 8Hz), 9.06 (lH, s)

Example 22 (6)

6- (2- (N-tert-butylsulfamoyl) phenyl)-1- (4-methoxybenzoyl) 13-formylindole (Compound 241)

Properties: colorless powder

Melting point: 163-165 ° C

_{'H-NMR (CDC1 3)} δ: 1.08 (9Η, s), 3.68 (IH, s), 3.94 (3H, s), 7.08 (2H, d, J = 9Hz), 7.32-7.38 (IH, m) , 7.46-7.59 (3H, m), 7.81 (2H, d, J = 9Hz), 8.08 (IH, s),

8.19 (1H, d, J = 9Hz), 8.38 (IH, d, J = 9Hz), 8.43 (IH, s), 10.12 (1H, s)

Example 22 (7)

5- (2- (N-tert-butylsulfamoyl) phenyl) — 1- (4-methoxybenzoyl) — 3-phenylsulfonylindole (Compound 242) Properties: colorless powder

Melting point: 208—210 ° C

_{'H-NMR (CDC1 3)} δ: 0.94 (9Η, s), 3.44 (IH, s), 3.96 (3H, s), 7.09 (2H, d, J = 9Hz), 7.32-7.34 (IH, m) , 7.49-7.61 (6H, m), 7.79 (2H, d, J = 9Hz), 8.05-8.08 (3H, m), 8.13 (1H, s), 8.20-8.21 (IH, s), 8.31 (IH, d, J = 8Hz)

Example 22 (8)

5- (2- (N-tert-butylsulfamoyl) phenyl) — 1— (4-methoxybenzoyl) _3- (2-pyridylsulfonyl) indole (Compound 243)

Properties: colorless powder

Melting point: 198—20 1 ° C

_{'H-NMR (CDC1 3)} δ: 1.02 (9Η, s), 3.95 (3H, s), 7.08 (2H, d, J = 9Hz),

7.35 (IH, d, J = 8Hz), 7.46-7.54 (2H, m), 7.54-7.61 (2H, m), 7.80 (2H, d, J = 9Hz), 7.91-7.98 (IH, m), 8.20 (IH, d, J-8Hz), 8.24 (2H, s), 8.26 (1H, d, J = 8Hz), 8.33 (lH, d, J = 8Hz) , 8.68 (lH, s)

Example 22 (9)

5-(2-(N-tert-butylsulfamoyl) phenyl) _ 1 _ (4-methoxybenzoyl) 13_ (4-methylphenylsulfonyl) indole (Compound 244)

Properties: colorless powder

Melting point: 1 96—199 ° C

_{'H-NMR (CDC1 3)} δ: 0.95 (9Η, s), 2.38 (3Η, s), 3.47 (IH, s), 3.95 (3H, s), 7.08 (2H, d, J = 9Hz), 7.29 (2H, d, J = 9Hz), 7.33 (IH, d, J = 7Hz), 7.50-7.56 (IH, m), 7.56-7.62 (2H, m), 7.79 (2H, d, J = 9Hz), 7.93 (2H, d, J = 8Hz), 8.07 (IH, s),

8.10 (IH, s), 8.20 (IH, d, J = 8Hz), 8.30 (1H, d, J = 9Hz)

Example 22 (10)

5- (2- (N-tert-butylsulfamoyl) phenyl) —3- (4-chlorophenylsulfonyl) _1- (4-methoxybenzoyl) indole (Compound 245)

Properties: brown amorphous

_{'H-NMR (CDC1 3)} δ: 0.98 (9Η, s), 3.44 (1H, s), 3.96 (3Η, s), 7.09 (2Η, d, J = 9Hz),

7.33 (IH, d, J = 6Hz), 7.48 (2H, d, J = 9Hz), 7.50-7.62 (3H, m), 7.78 (2H, d, J = 9Hz),

8.01 (2H, d, J = 9Hz), 8.09-8.12 (2H, m), 8.21 (1H, d, J = 8Hz), 8.32 (IH, d, J = 9Hz) Example 22 (1 1)

5- (2- (N-tert-butylsulfamoyl) phenyl) 1-1_ (4-dimethylaminobenzoyl) -1-2-methyl-3-phenylsulfonylindole (Compound 246)

Properties: colorless powder

Melting point: 224—227 ° C _{'H-NMR (CDC1 3)} δ: 0.93 (9H, s), 2.77 (3H, s), 3.13 (6H, s), 3.40 (IH, s),

6.65 (2H, d, J = 9Hz), 7.15 (1H, d, J = 9Hz), 7.35-7.39 (2H, m), 7.46-7.52 (3H, m),

7.52-7.64 (4H, m), 8.04 (2H, d, J = 7Hz), 8.18 (IH, d, J = 7Hz), 8.23 (1H, s) Example 22 (12)

5- (2- (N-tert-butylsulfamoyl) phenyl) — 1— (3-Dimethylaminobenzoyl) 1-Methyl-3-phenylsulfonylindole

(Compound 247)

Properties: yellow powder

Melting point: 200—202 ° C

'H-NMR (CDC1 ₃ ) δ 0.95 (9Η, s), 2.77 (3Η, s), 3.01 (6), s), 3.46 (IH, s),

6.88 (IH, d, J = 8Hz), 7.01 (IH, d, J = 9Hz), 7.08-7.15 (2H, m), 7.28-7.32 (1H, m),

7.32-7.39 (2H, m), 7.48-7.54 (2H, m), 7.54-7.61 (2H, m), 8.05 (2H, d, J = 8Hz), 8.18 (1H, d, J = 7Hz), 8.25 (1H, s)

Example 22 (13)

5- (2- (N-tert-butylsulfamoyl) phenyl) _ 1_ (3-dimethylaminobenzoyl) 1 3_ (2-pyridylsulfonyl) indole (Compound 248)

Properties: yellow oil

_{'H-NMR (CDC1 3)} <5: 1.03 (9H, s), 3.04 (6H, s), 4.01 (IH, s), 6.97-7.03 (3H, m),

7.35 (IH, d, J = 8Hz), 7.40 (IH, t, J = 8Hz), 7.45-7.61 (4H, m), 7.91-7.98 (IH, m),

8.20 (IH, d, J = 8Hz), 8.23-8.28 (3H, m), 8.43 (1H, d, J = 9Hz), 8.68 (1H, s) Example 22 (14)

5- (4-Formylphenyl) 1-1- (4-methoxybenzoyl) -13-phenylsulfonylindole (Compound 249)

Properties: colorless powder

Melting point: 240—242 ° C _{'H-NMR (CDC1 3)} δ: 3.65 (3H, s), 7.09 (2H, d, J = 9Hz), 7.50-7.54 (2H, m),

7.56-7.59 (1H, m), 7.71 (IH, dd, J = 9Hz, J = 2Hz), 7.77-7.82 (4H, m),

8.00 (2H, d, J = 9Hz), 8.02-8.06 (2H, m), 8.14 (1H, s), 8.16 (IH, d, J = 2Hz),

8.36 (lH, d, J = 9Hz), 10.10 (1H, s)

Example 22 (15)

5- (2- (1-tert-butyl- 1H-tetrazole-5-yl) phenyl) _1_ (4-dimethylaminobenzoyl) -3-3-phenylsulfonylindole (Compound 250)

Properties: colorless powder

Melting point: 182-185 ° C

_{'H-NMR (CDC1 3)} δ: 1.48 (9Η, s), 3.13 (6H, s), 6.75 (2H, d, J = 9Hz),

7.43-7.58 (7H, m), 7.68-7.75 (3H, m), 7.92-7.98 (3H, m), 7.70 (IH, d, J-9Hz), 8.14 (1H, s)

Example 22 (16)

5- (2- (N-tert-butylsulfamoyl) phenyl) _3_phenylthio 1-indolecarboxylic acid tert-butyl (Compound 251)

Properties: colorless amorphous

_{'H-NMR (CDC1 3)} δ: 0.89 (9Η, s), 1.71 (9H, s), 3.45 (1H, s), 7.09-7.13 (1H, m), 7.15-7.20 (3H, m), 7.22 -7.28 (1H, m), 7.41-7.55 (3H, m), 7.55-7.60 (2H, m), 7.95 (1H, s), 8.14 (IH, d, J = 9Hz), 8.20-8.27 (IH, m)

Example 22 (17)

5- (2- (N-tert-butylsulfamoyl) phenyl) -2-methyl-3-1-phenylthio-1-indolecarboxylic acid tert-butyl (Compound 252)

Properties: colorless powder

Melting point: 182-184 ° C _{'H-NMR (CDC1 3)} 6: 0.87 (9H, s), 1.74 (9H, s), 2.80 (3H, s), 3.48 (IH, s), 7.03-7.09 (3H, m), 7.16 (2H , T, J = 8Hz), 7.5-5.29 (IH, m), 7.45 (IH, t, J = 8Hz), 7.48-7.58 (4H, m), 8.14 (IH, d, J = 8Hz), 8.18 (1H, d, J = 8Hz)

Example 22 (18)

5- (2- (N_tert-butylsulfamoyl) phenyl) _3_ (2-pyridylthio) — 1_indolecarboxylate tert-butyl (Compound 253) Properties: colorless powder

Melting point: 1 75— 177

_{'H-NMR (CDC1 3)} δ 0.93 (9Η, s), 1.71 (9H, s), 3.53 (IH, s), 6.93-7.00 (2H, m),

7.22-7.30 (IH, m), 7.41-7.48 (2H, m), 7.52 (IH, t, J = 8Hz), 7.59-7.62 (2H, m),

8.02 (IH, s), 8.14 (1H, d, J = 8Hz), 8.24-8.29 (IH, m), 8.36—8.38 (IH, m) Example 22 (19)

5- (2- (N-tert-butylsulfamoyl) phenyl) -2-methyl-3- (2-pyridylthio) -tert-butyl 1-indolecarboxylate (Compound 254)

Properties: colorless powder

Melting point: 193-194V

'H-NMR (CDC1 ₃ ) 6: 0.91 (9H, s), 1.74 (9H, s), 2.79 (3, s), 3.54 (IH, s),

6.78 (1H, d, J = 9Hz), 6.94-6.99 (IH, m), 7.24-7.29 (IH, m), 7.38-7.57 (4H, m),

7.58 (IH, s), 8.14 (1H, d, J = 8Hz), 8.21 (IH, d, J = 9Hz), 8.38 (1H, d, J = 4Hz) Example 22 (20)

5- (3-pyridyl) _3- (2-pyridylthio) 1-1_indolecarboxylic acid tert-butyl (Compound 255)

Property: pale yellow amorphous

_{'H-NMR (CDC1 3)} δ: 1.71 (9Η, s), 6.91 (IH, d, J = 9Hz), 6.98-7.01 (IH, m), 7.32 (IH, dd, J = 6Hz, J = 5Hz ), 7.41 (IH, t, J = 7Hz), 7.59-7.63 (IH, m), 7.69 (1H, d, J-2Hz), 7.83-7.89 (1H, m), 8.00 (1H, s), 8.32 (1H, d, J = 8Hz),

8.41 (1H, d, J = 4Hz), 8.55 (1H, d, J = 3Hz), 8.82 (1H, d, J = 3Hz)

Example 22 (2 1)

2- (1-t-butoxycarbonyl-5- (2- (N-tert-butylsulfamoyl) phenyl)-2-methylindole-3-ylthio) benzyl benzoate (Compound 256)

Properties: colorless powder

Melting point: 88—91 ° C

_{'H-NMR (CDC1 3)} δ: 0.87 (9H, s), 1.74 (9H, s), 2.75 (3H, s), 3.52 (1H, s), 5.42 (2H, s), 6.76 (1H, d , J = 8Hz), 7.08 (1H, t, J = 7Hz), 7.15-7.21 (1H, m), 7.21-7.29 (1H, m), 7.32-7.46 (3H, m), 7.46-7.51 (4H, m), 7.58 (1H, d, J = 9Hz), 7.90 (1H, d, J = 8Hz), 8.07 (1H, d, J = 8Hz), 8.13 (1H, d, J = 8Hz), 8.21 (1H , d, J = 9 Hz) Example 23 (1)

5- (2- (N_tert-butylsulfamoyl) phenyl) —3-phenylsulfonylindole (Compound 257)

Dissolve 0.59 g of tert-butyl 5- (2- (N-tert-butylsulfamoyl) phenyl) -3-phenylthio-1-indolecarboxylate in 5 ml of methylene chloride and 0.47 g of MCPBA Was added and stirred at room temperature for 4 hours. The reaction solution was washed with an aqueous solution of sodium thiosulfate and an aqueous solution of sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated.

The residue was dissolved in 5 ml of tetrahydrofuran, 2 ml of 4% sodium hydroxide was added, and the mixture was stirred at 80 ° C for 5 hours. The reaction solution was concentrated, neutralized with 0.5% hydrochloric acid, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated. The residue was washed with hexane to obtain 0.38 g of the above compound as a light brown powder.

Properties: light brown powder

Melting point: 2 15-2 18 ° C _{'H-NMR (CDC1 3)} δ: 0.88 (9H, s), 3.44 (IH, s), 7.35 (IH, d, J = 8Hz),

7.41 (1H, d, J = 9Hz), 7.44-7.54 (5H, m), 7.57-7.60 (IH, m), 7.95 (IH, d, J = 3Hz),

8.00 (IH, s), 8.02-8.06 (2H, m), 8.19 (IH, d, J = 8Hz), 9.07 (IH, brs)

Example 23 (2) — (6)

The following (Compound 258) — (Compound 262) was obtained in the same manner as in Example 23 (1).

Example 23 (2)

5- (2- (N_tert-butylsulfamoyl) phenyl) -1-2-Methyl-3-phenylsulfonylindole (Compound 258)

Properties: brown powder

Melting point: 231— 233 ° C

_{Ή-NMR (CDC1 3) δ} : 0.93 (9Η, s), 2.78 (3H, s), 3.52 (IH, s), 7.22-7.28 (IH, m), 7.37 (1H, d, J = 7Hz), 7.40-7.53 (5H, m), 7.57-7.60 (IH, m), 7.99 (2H, d, J = 8Hz), 8.10 (lH, s), 8.19 (lH, d, J = 8Hz), 8.87 (IH , brs)

Example 23 (3)

5- (2- (N-tert-butylsulfamoyl) phenyl) -3- (2-pyridylsulfonyl) indole (Compound 259)

Properties: colorless powder

Melting point: 265 _ 266

_{'H-NMR (CDC1 3)} δ: 1.20 (9Η, s), 4.32 (IH, s), 7.12 (1H, d, J = 3Hz),

7.28-7.30 (IH, m), 7.34 (IH, d, J = 7Hz), 7.42-7.45 (IH, m), 7.45-7.53 (IH, m),

7.53-7.60 (IH, m), 7.82 (IH, d, J = 8Hz), 7.93 (IH, dd, J = 9Hz, 2Hz),

8.20 (IH, d, J = 3Hz), 8.23 (IH, s), 8.25-8.29 (IH, m), 8.68 (IH, d, J = 5Hz),

9.39 (lH, brs)

Example 23 (4)

5- (2- (N—tert-butylsulfamoyl) phenyl) _2—methyl— 3- (2-pyridylsulfonyl) indole (Compound 260) Properties: light brown powder

Melting point: 245—247 ° C

_{'H-NMR (CDC1 3)} δ: 1.05 (9Η, s), 2.71 (3Η, s), 4.65 (IH, s), 6.73 (IH, d, J = 9Hz), 7.11 (1H, d, J = 7 Hz), 7.34 (IH, d, J = 7 Hz), 7.41-7.46 (IH, m), 7.49 (IH, t, J = 7 Hz), 7.57 (IH, t, J = 8 Hz), 7.91 (1H, dd) , J = 6Hz, 5Hz), 8.21 (IH, d, J = 8Hz), 8.25 (1H, s), 8.68 (lH, d, J = 5Hz), 8.94 (1H, s)

Example 23 (5)

2- (5- (2-((N_tert-butylsulfamoyl) phenyl) -2-methylindole-3-ylsulfonyl) Benzyl benzoate (Compound 261) Properties: Brown powder

Melting point: 1 18- 1201

_{'H-NMR (CDC1 3)} δ: 0.92 (9Η, s), 2.67 (3Η, s), 3.67 (IH, s), 5.28 (2H, s),

7.22-7.30 (IH, m), 7.30-7.38 (4H, m), 7.38-7.44 (3H, m), 7.44-7.58 (5H, m),

8.00 (IH, s), 8.08-8.11 (IH, m), 8.17 (1H, d, J = 8Hz), 8.70 (IH, brs)

Example 23 (6)

5-(3-pyridyl) _ 3 _ (2-pyridylsulfonyl) indole (Compound 262)

Properties: colorless powder

Melting point: 270 ° C (dec.)

'H-NMR (DMS0-d ₆ ) δ: 7.51-7.55 (IH, m), 7.58-7.66 (4H, m), 8.06-8.12 (2H, m), 8.23 (IH, d, J = 7 Hz), 8.27 (IH, d, J = 8Hz), 8.29 (1H, s), 8.47 (IH, s),

8.66 (1H, d, J = 4Hz)

Example 24 (1)

Synthesis of 1- (3-dimethylaminobenzoyl) -3-phenylsulfonyl-5- (2-sulfamoylphenyl) indole (Compound 263) 5- (2- (N-tert-butylsulfamoyl) phenyl) _3_phenylsulfonylindole (94 mg) was dissolved in 4 ml of tetrahydrofuran, and the mixture was dissolved in 0.1 ml of diisopropylethylamine and 3 dimethylaminoamine. Nzoyl chloride 70018 was stirred at 30 ^ for 70 hours. A 4% aqueous sodium hydroxide solution was added to the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to column chromatography (silica gel; hexane Z ethyl acetate = 41). The obtained compound was dissolved in 2 ml of trifluoroacetic acid and stirred at room temperature for 1 day. The reaction solution was concentrated, neutralized with a saturated aqueous solution of sodium carbonate, and extracted with ethyl acetate. After drying over magnesium sulfate anhydride and concentrating, 24 mg of the above compound was obtained.

Properties: yellow powder

Melting point: 124- 126 ° C

'Η-NMR (CDC1 ₃ ) δ 3.05 (6Η, s), 4.20 (2Η, s), 6.99-7.04 (3Η, m),

7.38 (1Η, d, J = 7Hz), 7.40-7.45 (IH, m), 7.48-7.60 (5H, m), 7.63-7.67 (IH, m),

8.01-8.04 (2H, m), 8.09 (IH, s), 8.16 (1H, s), 8.21 (IH, d, J = 7Hz),

8.44 (lH, d, J = 9Hz)

Example 24 (2) One (9)

The following (Compound 264)-(Compound 271) were obtained in the same manner as in Example 24 (1).

Example 24 (2)

1- (3-Dimethylamino-2-methylbenzoyl) -1_3-phenylsulfonyl-1_5_ (2-Sulfamoylphenyl) indole (Compound 264)

Properties: colorless powder

Melting point: 200—203

_{'H-NMR (CDC1 3)} δ: 2.31 (3H, s), 2.80 (6H, s), 4.20 (2Η, s), 7.07 (IH, d, J = 6Hz),

7.28-7.37 (3H, m), 7.49-7.59 (5H, m), 7.62-7.66 (IH, m), 7.83 (IH, s),

8.01 (2H, d, J = 7Hz), 8.06 (IH, s), 8.21 (IH, d, J = 7Hz), 8.49 (IH, d, J = 8Hz) Example 24 (3)

1- (3-Chloro-2-methylbenzoyl) — 3 _phenylsulfonyl-5- (2-sulfamoylphenyl) indole (Compound 265)

Properties: pale yellow powder

Melting point: 231-234 ° C

_{'H-NMR (CDC1 3)} δ: 2.40 (3Η, s), 4.23 (2Η, s), 7.30-7.39 (3Η, m),

7.50-7.60 (5Η, m), 7.65 (2Η, t, J = 8Hz), 7.75 (1H, s), 8.02 (2H, d, J = 7Hz),

8.07 (1H, s), 8.20 (IH, d, J = 9Hz), 8.50 (1H, d, J = 9Hz)

Example 24 (4)

1- (3-Methoxy-2-methylbenzoyl) -3-phenylsulfonyl-5- (2-Sulfamoylphenyl) indole (Compound 266)

Properties: light brown powder

Melting point: 223-2261

_{'H-NMR (CDC1 3)} δ: 2.21 (3Η, s), 3.95 (3Η, s), 4.20 (2Η, s), 7.00 (IH, d, J = 8Hz), 7.09 (1H, d, J = 8Hz), 7.32-7.39 (2H, m), 7.48-7.60 (5H, m), 7.64 (IH, t, J = 7Hz), 7.80 (IH, s), 8.01 (IH, d, J = 7Hz), 8.05 (IH, s), 8.20 (IH, d, J = 7Hz),

8.51 (lH, d, J = 9Hz)

Example 24 (5)

1- (3-Dimethylamino-2-methylbenzoyl) -3- (2-pyridylsulfonyl) -5- (2-sulfamoylphenyl) indole (Compound 267) Properties: Light brown powder

Melting point: 219 _ 222 ° C

_{'H-NMR (CDC1 3)} δ: 2.30 (3Η, s), 2.77 (6Η, s), 4.91 (2Η, s), 7.05 (IH, d, J = 6Hz), 7.22-7.32 (2H, m) , 7.40 (1H, d, J = 8Hz), 7.47-7.58 (3H, m), 7.63 (1H, d, J = 6Hz),

7.86 (IH, s), 7.91-7.97 (IH, m), 8.18-8.21 (2H, m), 8.32 (IH, s), 8.50 (IH, d, J = 9Hz),

8.66 (1H, d, J = 5Hz) Example 24 (6)

1- (3-methoxy-2-methylbenzoyl)-3- (2-pyridylsulfonyl) -1-5- (2-sulfamoylphenyl) indole (Compound 268) Properties: light brown powder

Melting point: 235— 237 ° C

_{'H-NMR (CDC1 3)} δ: 2.19 (3Η, s), 3.93 (3Η, s), 4.92 (2Η, s), 6.98 (IH, d, J = 8Hz), 7.07 (1H, d, J = 8Hz), 7.34 (1H, t, J = 8Hz), 7.40 (1H, d, J = 6Hz), 7.49 (1H, t, J = 6Hz),

7.51-7.58 (2H, m), 7.64 (IH, t, J = 7Hz), 7.82 (IH, s), 7.94 (IH, t, J = 8Hz),

8.20 (2H, t, J = 7Hz), 8.33 (1H, s), 8.52 (IH, d, J = 9Hz), 8.67 (IH, d, J = 5Hz) Example 24 (7)

1- (2,4-dimethoxybenzoyl) —3 -— (2-pyridylsulfonyl) _5-(2-sulfamoylphenyl) indole (Compound 269)

Properties: light brown powder

Melting point: 135-138

_{'H-NMR (CDC1 3)} δ: 3.75 (3Η, s), 3.92 (3Η, s), 4.84 (2H, s), 6.56 (IH, s),

6.64 (IH, d, J = 9Hz), 7.38-7.41 (IH, m), 7.41-7.58 (4H, m), 7.63 (IH, t, J = 8Hz),

7.90-7.98 (2H, m), 8.20 (2H, t, J = 8Hz), 8.23 (IH, s), 8.47 (IH, d, J = 9Hz),

8.65 (1H, s)

Example 24 (8)

1- (2,6-dimethoxynicotinol) —3- (2-pyridylsulfonyl) — 5- (2-sulfamoylphenyl) indole (compound 270)

Properties: light brown powder

Melting point: 233—236

_{'H-NMR (CDC1 3)} δ: 3.91 (3Η, s), 4.05 (3Η, s), 4.84 (2H, s), 6.51 (IH, d, J = 9Hz), 7.40 (IH, d, J = 7Hz), 7.47-7.58 (3H, m), 7.60-7.65 (IH, m), 7.84 (IH, d, J = 8Hz), 7.90-7.95 (IH, m), 7.98 (1H, s), 8.18- 8 · 22 (2H, m), 8.28 (IH, d, J = lHz), 8.46 (lH, d, J = 9Hz), 8.66 (1H, d, J = 4Hz)

Example 24 (9)

1- (3-Dimethylamino-2-methylbenzoyl) -1-5- (3-pyridyl)-3- (2-pyridylsulfonyl) indole (Compound 27 1)

Properties: pale yellow powder

Melting point: 225—228 ° C

_{'H-NMR (CDC1 3)} δ: 2.28 (3Η, s), 2.78 (6H, s), 7.08 (IH, d, J = 7Hz),

7.28-7.36 (2H, m), 7.38 (IH, t, J = 7Hz), 7.46-7.51 (IH, m), 7.55 (IH, d, J = 8Hz),

7.62 (1H, d, J = 9Hz), 7.94-8.00 (2H, m), 8.20-8.28 (3H, m), 8.52 (1H, s),

8.54 (1H, d, J = 9Hz), 8.66 (IH, d, J = 5Hz)

Example 25 (1)

1- (3-Dimethylamino-2-methylbenzoyl) 1-2-methyl-3-phenylsulfonyl-5- (2-sulfamoylphenyl) indole (Compound 272)

5- (2_ (N-tert-butylsulfamoyl) phenyl) -2-methyl-3-phenylsulfonylindole 9 Omg is dissolved in 4 ml of tetrahydrofuran, and sodium hydride (60%) 2 Omg under ice cooling. 89 mg of, 3-dimethylamino-2 monomethylbenzoyl chloride was added, and the mixture was stirred at room temperature for 5 hours and at 60 ° C for 1 hour. A 4% aqueous sodium hydroxide solution was added to the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to column chromatography (silica gel; ethyl hexanoacetate = 41).

The residue was dissolved in 2 ml of trifluoroacetic acid and stirred at room temperature for 3 days. The reaction solution was concentrated, neutralized with a saturated aqueous solution of sodium carbonate, and extracted with ethyl acetate. After drying with anhydrous magnesium sulfate and concentration, 44 mg of the above compound was obtained.

Properties: yellow powder

Melting point: 1 18 _ 12 1 ° C _{'H-NMR (CDC1 3)} 6: 2.29 (3H, s), 2.70 (3H, s), 2.73 (6H, s), 4.26 (2H, s), 7.00-7.03 (IH, m), 7.12 (IH , d, J = 9Hz), 7.21-7.31 (3H, m), 7.34-7.39 (IH, m), 7.49-7.65 (5H, m), 8.01 (2H, d, J = 8Hz), 8.18 (1H, d, J = 8Hz), 8.26 (IH, s) Example 25 (2)-(6)

The following (Compound 273) — (Compound 277) were obtained in the same manner as in Example 25 (1).

Example 25 (2)

1- (2,4-dimethoxybenzoyl) — 2-methyl_ 3 _phenylsulfonyl-5- (2-sulfamoylphenyl) indole (Compound 273)

Properties: colorless powder

Melting point: 123-126 ° C

_{'H-NMR (CDC1 3)} 6: 2.74 (3H, s), 3.42 (3Η, s), 3.90 (3H, s), 4.26 (2H, s),

6.40 (IH, d, J = 2 Hz), 6.62 (IH, dd, J = 8 Hz, J = 2 Hz), 7.19 (1H, d, J = 9 Hz),

7.21-7.28 (IH, m), 7.39 (1H, d, J = 6Hz), 7.44-7.59 (4H, m), 7.59-7.67 (2H, m),

7.97-8.02 (2H, m), 8.17 (IH, d, J = 8Hz), 8.23 (IH, s)

Example 25 (3)

1- (3-Methoxy-2-methylbenzoyl) — 2-methyl-3-phenylsulfonyl-5- (2-sulfamoylphenyl) indole (Compound 274) Properties: Light brown powder

Melting point: 128- 131 ° C

'H-NMR (CDC1 ₃ ) δ 2.24 (3Η, s), 2.69 (3Η, s), 3.91 (3Η, s), 4.26 (2Η, s),

6.92 (IH, d, J = 8Hz), 7.09 (1H, d, J = 8Hz), 7.18 (1H, d, J = 8Hz), 7.21-7.30 (1H, m),

7.36 (IH, d, J = 8Hz), 7.48-7.62 (6H, m), 8.01 (2H, d, J = 8Hz), 8.19 (1H, d, J = 7Hz), 8.27 (lH, s)

Example 25 (4)

1- (3-dimethylamino-2-methylbenzoyl) _2-methyl_3_ (2- Pyridylsulfonyl) -5- (2-sulfamoylphenyl) indole (Compound 275)

Properties: pale yellow powder

Melting point: 122-125

_{'H-NMR (CDC1 3)} δ: 2.28 (3Η, s), 2.71 (3Η, s), 2.73 (6Η, s), 5.08 (2Η, s),

7.03 (1Η, d, J = 8Hz), 7.08 (1Η, d, J = 9Hz), 7.18—7.21 (IH, m), 7.21-7.30 (2H, m),

7.36 (1H, d, J-7Hz), 7.46-7.53 (2H, m), 7.57-7.61 (1H, m), 8.17-8.22 (2H, m),

8.42 (1H, d, J = 2Hz), 8.65 (1H, d, J = 5Hz)

Example 25 (5)

1- (2,6-dimethoxynicotinol) -1-2-methyl_3_ (2-pyridylsulfonyl) — 5_ (2-sulfamoylphenyl) indole (Compound 276) Properties: brown powder

Melting point: 123-125

_{'H-NMR (CDC1 3)} δ: 2.75 (3Η, s), 3.62 (3H, s), 4.00 (3Η, s), 5.08 (2Η, s),

6.47 (IH, d, J = 8Hz), 7.22 (1H, s), 7.39 (IH, d, J = 8Hz), 7.46-7.54 (2H, m),

7.60 (1H, t, J = 8Hz), 7.90-7.98 (2H, m), 8.18 (IH, d, J = 8Hz), 8.22 (IH, d, J = 8Hz), 8.40 (1H, s), 8.64 (1H, s)

Example 25 (6)

2- (1- (3-Dimethylamino-1-methylbenzoyl) -1-5_ (2-sulfamoylphenyl) -1-methylindole-3-ylsulfonyl) Benzyl benzoate (Compound 277)

Properties: yellow powder

Melting point: 130_ 132t:

_{'H-NMR (CDC1 3)} δ: 2.32 (3Η, s), 2.49 (3Η, s), 2.88 (6Η, s), 4.60 (2Η, brs), 5.06 (2Η, s), 7.05 (1Η, d , J = 9Hz), 7.09 (IH, d, J = 8Hz), 7.21-7.34 (8H, m),

7.39 (1H, d, J = 8Hz), 7.48-7.54 (IH, m), 7.54-7.67 (4H, m), 8.14 (lH, s), 8.16 (lH, d, J = 9Hz), 8.22 (1H, d, J = 7Hz)

Example 2 6 (1)

5- (2-sulfamoylphenyl) 1-1- (4-methoxybenzoyl) 1-3-formylindole (compound 278)

5- (2- (N-tert-butylsulfamoyl) phenyl) 1-1- (4-methoxybenzoyl) 13-formylindole 0.57 g was dissolved in 12 ml of trifluoroacetic acid, Stir for 7 hours. The reaction solution was concentrated, a saturated aqueous solution of sodium hydrogen carbonate was added, and the mixture was extracted with chloroform. After drying over anhydrous magnesium sulfate, it was concentrated. The residue was subjected to column chromatography (silica gel; black form) to give 4 Omg of the above compound.

Properties: colorless powder

Melting point: 20 7—2 1 0

'H-NMR (CDC1 ₃ ) δ 3.95 (3Η, s), 4.03 (2Η, s), 7.10 (2H, d, J = 9Hz),

7.43 (1H, d, J = 7Hz), 7.52-7.69 (3H, m), 7.83 (2H, d, J = 9Hz), 8.ll (lH, s),

8.20 (1H, d, J = 7Hz), 8.32 (1H, d, J = 9Hz), 8.38 (1H, s), 10.08 (1H, s)

Example 26 (2) — (6)

The following (Compound 2779)-(Compound 283) was obtained in the same manner as in Example 26 (1).

Example 26 (2)

5- (2-Sulfamoylphenyl) -1- (4-methoxybenzoyl) _3- (2-pyridylsulfonyl) indole (Compound 2 79)

Properties: colorless powder

Melting point: 2 24— 2 2 7:

_{'H-NMR (CDC1 3)} δ: 3.94 (3Η, s), 4.89 (2Η, s), 7.07 (2Η, d, J = 9Hz),

7.41 (1H, d, J = 7Hz), 7.48-7.57 (3H, m), 7.61-7.66 (1H, m), 7.78 (2H, d, J = 9Hz),

7.95 (1H, t, J = 7Hz), 8.16 (1H, s), 8.18-8.24 (2H, m), 8.32 (1H, s), 8.35 (lH, d, J = 9Hz), 8.62-8.68 (lH, m)

Example 26 (3)

5-(2-Sulfamoylphenyl)-1-(4-methoxybenzoyl) _3-(4-Methylphenylsulfonyl) indole (Compound 280)

Properties: colorless powder

Melting point: 205—207 ° C

E - thigh _{(CDC1 3) δ: 2.39 (} 3Η, s), 3.96 (3Η, s), 4.23 (2H, s), 7.09 (2H, d, J = 9Hz), 7.29 (2H, d, J = 9Hz ), 7.37 (IH, d, J = 7Hz), 7.50-7.58 (2H, m), 7.61-7.65 (1H, m),

7.79 (2H, d, J = 9Hz), 7.91 (1H, d, J = 9Hz), 8.09 (1H, s), 8.10 (IH, s),

8.21 (IH, d, J = 7Hz), 8.34 (IH, d, J = 9Hz)

Example 26 (4)

5— (2-Sulfamoylphenyl) — 1— (4-Dimethylaminobenzoyl) 1 2 _methyl -3- 3-phenylsulfonylindole (Compound 281)

Properties: yellow powder

Melting point: 138-140

_{'H-NMR (CDC1 3)} 6 2.75 (3H, s), 3.13 (6H, s), 4.28 (2Η, s), 6.67 (2H, d, J = 9Hz), 7.18-7.25 (2H, m), 7.25-7.30 (1H, m), 7.39 (IH, d, J = 9Hz), 7.46-7.58 (3H, m), 7.58-7.68 (3H, m), 8.03 (2H, d, J = 9Hz), 8.20 (1H, d, J = 9Hz), 8.24 (IH, s) Example 26 (5)

5- (2-Sulfamoylphenyl) -1- (3-dimethylaminobenzyl) _2-Methyl_3-phenylsulfonylindole (Compound 282)

Properties: yellow powder

Melting point: 122-125

_{'H-NMR (CDC1 3)} δ: 2.75 (3Η, s), 3.00 (6Η, s), 4.27 (2H, s), 6.93 (IH, d, J = 8Hz),

7.01 (IH, d, J = 8Hz), 7.09 (IH, s), 7.18 (1H, d, J = 9Hz), 7.21-7.30 (1H, m),

7.32 (1H, t, J = 8Hz), 7.38 (1H, d, J = 7Hz), 7.49-7.65 (5H, m), 8.03 (2H, d, J = 8Hz), 8.18 (lH, d, J = 8Hz), 8.25 (lH, s)

Example 26 (6)

5- (2-Sulfamoylphenyl) 1-1_ (3-dimethylaminobenzyl) —3- (2-pyridylsulfonyl) indole (Compound 283)

Properties: yellow powder

Melting point: 133-1 35 ° C

_{'H-NMR (CDC1 3)} δ: 3.03 (6Η, s), 4.91 (2Η, s), 6.96-7.01 (3Η, m),

7.38-7.42 (2Η, m), 7.45-7.59 (3H, m), 7.64 (IH, t, J = 8Hz), 7.94 (1H, t, J = 6Hz), 8.15—8.24 (3H, m), 8.33 (IH, s), 8.45 (1H, d, J = 9Hz), 8.66 (IH, d, J = 4Hz)

2- (1- (3-dimethylamino-2-methylbenzoyl) — 5- (2-sulfamoylphenyl) -1-methylindole-3-ylsulfonyl) benzoic acid (Compound 284)

2- (1— (3-Dimethylamino_2-methylbenzoyl) -1- (2-sulfamoylphenyl) —2-methylindole-3-ylsulfonyl) Dissolve 0.29 g of benzyl benzoate in 8 ml of methanol and water 0.12 g of palladium oxide on carbon was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 days. The catalyst was filtered, and the filtrate was concentrated to obtain 0.24 g of the above compound.

Properties: yellow powder

Melting point: 1 64— 168:

_{'H-NMR (CDC1 3)} δ: 2.18 (3H, s), 2.53 (3H, s), 2.66 (6H, s), 7.08 (IH, d, J = 9Hz), 7.13-7.19 (2H, m) , 7.26 (2H, t, J = 6 Hz), 7.34 (IH, t, J = 8 Hz), 7.39 (IH, d, J = 8 Hz), 7.57-7.68 (3H, m), 7.74 (IH, t, J = 7Hz), 7.90 (IH, s), 8.05 (IH, d, J = 8Hz), 8.14 (lH, d, J = 8Hz)

Example 28

5- (2- (N-acetylsulfamoyl) phenyl) 1 1 1 (4—dimethyla Minobenzyl) 1-Methyl-3-phenylsulfonylindole (Compound 285)

1- (4-Dimethylaminobenzoyl) 1-2-methyl-3-phenylsulfonyl-5- (2-sulfamoylphenyl) indole 4 Omg was dissolved in 2 ml of tetrahydrofuran, 4 mg of sodium hydride (60%), Acetyl chloride 61 was added and the mixture was stirred at room temperature for 6 hours. Water was added to the reaction solution, and the mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to column chromatography (silica gel; chloroform) to obtain 1 mg of the above compound.

Properties: pale yellow powder

Melting point: 144-146

_{'H-NMR (CDC1 3)} δ: 1.98 (3Η, s), 2.75 (3H, s), 3.13 (6Η, s), 6.66 (2Η, d, J = 9Hz), 7.12-7.20 (2H, m) , 7.39 (1H, d, J = 7Hz), 7.47-7.54 (2H, m), 7.54-7.61 (2H, m), 7.61-7.70 (3H, m), 8.00 (2H, d, J = 8Hz), 8.19 (1H, s), 8.40 (1H, d, J = 8Hz)

3 _dimethylamino_2 _methylbenzoic acid (Compound 286)

5 g of 3-amino-2-methylbenzoic acid and 13.7 potassium carbonate were added to 5 Om1 of ^, N-dimethylformamide, and 3 Oml of dimethyl sulfate was added dropwise at room temperature. The reaction was heated at 80 for 18 hours. Water was added to the reaction solution, extracted with getyl ether, dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (160 ml), 4% sodium hydroxide (70 ml) was added, and the mixture was refluxed for 2 days. The reaction solution was concentrated and neutralized with citric acid. The mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated to obtain 3.46 g of the title compound.

Properties: colorless powder

Melting point: 125-127 ° C

'H-NMR (DMSO-d ₆ ) δ 2.41 (3Η, s), 2.62 (6Η, s), 7.18-7.25 (2Η, m),

7.35-7.40 (1Η, m) Example 30 (1)

5-Hydroxy-1- (4-methoxybenzoyl) -1-3- (4-methylphenylsulfonyl) indole (Compound 287)

Dissolve 0.6 g of 5-benzyloxy 1- (4-methoxybenzoyl) -13- (4-methylphenylsulfonyl) indole in 2 ml of tetrahydrofuran and 4 ml of methanol. 15 g was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 1 day. The catalyst was filtered, and the filtrate was concentrated. The residue was subjected to column chromatography (silica gel; black form) to obtain 0.17 g of the above compound.

Properties: colorless powder

Melting point: 1 74 _ 176 ° C

_{'H-NMR (CDC1 3)} δ: 2.38 (3Η, s), 3.93 (3H, s), 5.48 (1Η, s), 6.94 (IH, d, J = 9Hz), 7.05 (2H, d, J = 9Hz), 7.28 (2H, d, J = 8Hz), 7.32 (IH, d, J = 3Hz), 7.74 (2H, d, J = 9Hz), 7.88 (2H, d, J = 8Hz), 8.01 (IH , s), 8.13 (IH, d, J = 8Hz)

Example 30 (2)

The following (Compound 288) was obtained in the same manner as in Example 30 (1).

1- (4-Dimethylaminobenzoyl) -5-hydroxy-3-phenylsulfonylindole (Compound 288)

Properties: pale yellow powder

Melting point: 197-200

_{'H-NMR (CDC1 3)} δ: 3.13 (6Η, s), 5.01 (IH, s), 6.74 (2H, d, J = 9Hz),

6.93 (IH, dd, J = 9Hz, J = 2Hz), 7.32 (IH, d, J = 2Hz), 7.47-7.51 (2H, m),

7.51-7.58 (1H, m), 7.70 (2H, d, J = 9Hz), 8.01 (2H, d, J = 8Hz), 8.07 (IH, d, J = 9Hz), 8.12 (lH, s)

Example 31 (1)

(1- (4-Methoxybenzoyl) -3- (4-methylphenylsulfonyl) indole-5-yl) ethyl oxyacetate (Compound 289) 5-Hydroxy-11- (4-methoxybenzoyl) -3- (4-methylphenylsulfonyl) Indole 5Omg was dissolved in tetrahydrofuran 2m1, sodium hydride (60%) 6mg, ethyl bromoacetate 201 was added and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated. The residue was triturated with hexane to obtain 52 mg of the above compound.

Properties: brown powder

Melting point: 20 1—204 ° C

_{'H-NMR (CDC1 3)} 6: 1.27 (3H, t, J = 7Hz), 2.37 (3H, s), 3.92 (3H, s),

4.24 (2H, q, J = 7Hz), 4.87 (2H, s), 7.01 (2H, d, J = 9Hz), 7.18 (1H, dd, J = 9Hz, J = 2Hz),

7.21-7.30 (3H, m), 7.75 (1H, d, J = 2Hz), 7.84 (1H, s), 7.89 (2H, d, J = 8Hz),

8.18 (2H, d, J = 9Hz)

Example 3 1 (2) One (3)

The following (Compound 290)-(Compound 291) were obtained in the same manner as in Example 31 (1).

Example 3 1 (2)

(1-(4-methoxybenzoyl) _3- (4-methylphenyl) sulfonylindole-5-yl) tert-butyl oxyacetate (Compound 290)

Properties: colorless powder

Melting point: 184-186 ° C

_{'H-NMR (CDC1 3)} δ: 1.44 (9Η, s), 2.36 (3Η, s), 3.92 (3Η, s), 4.76 (2Η, s),

7.01 (2Η, d, J = 9Hz), 7.18-7.20 (1H, m), 7.25-7.29 (3H, m), 7.75 (1H, s),

7.83 (1H, s), 7.89 (2H, d, J = 9Hz), 8.18 (2H, d, J = 9Hz)

Example 3 1 (3)

(1- (4-dimethylaminobenzoyl) -1-3-phenylsulfonylindole-1-5-yl) t-tert-butyl oxyacetate (Compound 291)

Properties: colorless powder Melting point: 107-109 ° C

_{'H-NMR (CDC1 3)} δ: 1.43 (9H, s), 3.10 (6H, s), 4.76 (2H, s), 6.72 (2H, d, J = 9Hz), 7.17-7.21 (2H, m) , 7.42-7.51 (3H, m), 7.76 (1H, d, J = 2Hz), 7.84 (IH, s),

7.99-8.02 (2H, m), 8.08 (2H, d, J = 9Hz)

Example 32 (1)

(1- (4-Methoxybenzoyl) -3- (4-methylphenylsulfonyl) indole-1-yl) oxyacetic acid (Compound 292)

(1- (4-Methoxybenzoyl) -3- (4-methylphenylsulfonyl) indole-5-yl) oxytertacetic acid tert-butyl 4 Omg was added with 2 ml of trifluoroacetic acid and stirred at room temperature for 1 day. The reaction solution was concentrated to obtain 3 Omg of the above compound. Properties: colorless powder

Melting point: 228—231 ° C.

■ H-NMR (DMS0-d ₆ ) δ 2.34 (3Η, s), 3.89 (3H, s), 5.18 (2H, s), 7.1 (2H, d, J = 9 Hz), 7.18 (1H, d, J = 9Hz), 7.38 (2H, d, J = 9Hz), 7.58-7.64 (2H, m), 7.86 (2H, d, J = 9Hz), 8.12 (2H, d, J = 9Hz), 8.29 (lH, s)

Example 32 (2)

The following (Compound 293) was obtained in the same manner as in Example 32 (1).

(1- (4-Dimethylaminobenzoyl) _3-phenylsulfonylindole-1-5-yl) oxyacetic acid (Compound 293)

Properties: colorless powder

Melting point: 265 ° C (dec.)

Ή-NMR (DMS0-d ₆ ) δ: 3.06 (6H, s), 4.59 (2H, s), 6.80 (2H, d, J = 9 Hz),

7.07 (1H, d, J = 9Hz), 7.43 (IH, d, J = 9Hz), 7.50-7.61 (4H, m), 7.91-7.98 (4H, m),

8.20 (1H, s)

Reference example 5 (1)

2- (2-oxopropylthio) benzyl nicotinate (Compound 294) 6.2 g of 2-mercaptonicotinic acid was added to 30 ml of DMF, 5.6 g of potassium carbonate was added, and the mixture was stirred at room temperature for 20 minutes. To the mixture was added 3.68 g of acetone, and the mixture was further stirred for 2 hours. 6.84 g of benzyl bromide was added, and the mixture was stirred at room temperature for 3 hours. Ethyl acetate (25 Oml) was added, and the mixture was washed with water 11.times.2 times. After drying, the organic layer was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel; dichloromethane). 6.3 g of the above compound was obtained.

Properties: yellow solid

Melting point: 64— 64. 51:

_{Ή-NMR (CDC1 3) (} 5: 2.32 (3H, s), 3.89 (2H, s), 5.37 (2H, s),

7.06 (1H, dd, J = 8Hz, J = 5Hz), 7.33-7.46 (5H, m), 8.26 (1H, dd, J = 8Hz, J = 2Hz), 8.47 (lH, dd, J = 5Hz, J = 2Hz)

Reference Example 5 (2) One (3)

The following (Compound 295) to (Compound 296) were synthesized in the same manner as in Reference Example 5 (1).

Reference example 5 (2)

6- (2-oxopropylthio) benzyl ester of nicotinic acid (Compound 295) Properties: yellow oil

_{Ή-NMR (CDC1 3) δ} : 2.34 (3H, s), 4.03 (2H, s), 5.36 (2H, s),

7.29 (1H, dd, J = 8Hz, J = lHz), 7.34-7.45 (5H, m), 8.09 (1H, dd, J = 8Hz, J = 2Hz) 9.01 (lH, dd, J = 2Hz, J = lHz)

Reference example 5 (3)

4- (2-oxopropylthio) benzoic acid benzyl ester (Compound 296) Properties: yellow oil

_{Ή-NMR (CDC1 3) δ} : 2.29 (3Η, s), 3.75 (2Η, s), 5.34 (2Η, s), 7.30 (2H, d, J = 8Hz), 7.34-7.44 (5H, m), 7.97 (2H, d, J = 8Hz)

Reference example 6 4- (2-oxopropylthio) phenyloxyacetic acid tert-butyl ester (Compound 297)

8.6 g of P-hydroxythiophenol and 6.4 g of acetone were dissolved in 120 ml of dichloromethane. Under ice cooling, 8.8 g of diisopropylethylamine / 10 ml of dichloromethane was added dropwise over 15 minutes. The mixture was stirred at the same temperature for 50 hours. It was washed with 100 ml of 3% citric acid. After drying, the solvent was distilled off under reduced pressure. Hexane was added to the residue, followed by filtration. 11.3 g of a yellow solid was obtained. This solid 5.468 and bromoacetic acid 6 t-butyl ester 5.858 were dissolved in 1, N-dimethylformamide 2 Om1, and 6.9 g of potassium carbonate was added. The mixture was stirred at room temperature for 3 hours. Ethyl acetate (10 Om1) was added, and the mixture was washed twice with 3% aqueous sodium carbonate (300 ml ×). After drying, the organic layer was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel; dichloromethane). 7.79 g of the above compound was obtained.

Properties: yellow oil

_{Ή-NMR (CDC1 3) δ} : 1.49 (9Η, s), 2.25 (3Η, s), 3.56 (2H, s), 4.48 (2H, s),

6.83 (2H, dd, J = 7Hz, J = 2Hz), 7.33 (2H, dd, J = 7Hz, J = 2Hz)

Reference Example 7

2- (2-oxopropylthio) benzoic acid benzyl ester (Compound 298) 1.45 g of 2- (2-oxopropylthio) benzoic acid synthesized in Reference Example 1 (3) was converted to N, N-dimethylform. The solution was dissolved in 5 ml of the amide, and 0.75 g of potassium carbonate and 0.85 g of benzylbutane were added. After stirring at room temperature for 6 hours, 5 Oml of ethyl acetate was added and the mixture was washed twice with 5 Oml of saturated aqueous sodium hydrogen carbonate. After drying, the organic layer was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel; dichloromethane). 1.12 g of the above compound was obtained. .

Properties: yellow oil

_{Ή-NMR (CDC1 3) δ} 2.30 (3H, s), 3.70 (2H, s), 5.37 (2H, s), 7.18 (1H, t, J = 8Hz),

7.29 (1H, d, J = 8Hz), 7.35 (1H, d, J = 8Hz), 7.37-7.47 (5H, m), 8.03 (1H, d, J = 8Hz) Reference Example 8

N-tert-butyl-2- (4'-tert-butoxycarbonylhydrazinophenyl) benzenesulfonamide (Compound 299)

N_ tert _ butoxycarbonyl one P- bromo-phenylalanine hydrazine 5. 8 g, N- tert- Petit Rusuru sulfamoyl phenylene Ruporon acid 5. 1 g, carbonate sodium _{4. 2 g, PdC 1 2 (} PPh 3) 2 0.5 g and trifenylphosphine (1.5 g) were added to toluene (100 ml) and water (30 ml), and the mixture was heated with stirring under a nitrogen atmosphere for 18 hours. 200 ml of ethyl acetate was added, and the mixture was washed with 300 ml of water. Insolubles dissolved in dichloromethan. The combined organic layers were dried and evaporated under reduced pressure. The residue was subjected to column chromatography (silica gel; dichloromethane / ethyl acetate = 20/1). 3.28 g of the above compound was obtained.

Properties: colorless powder

Melting point: 217—218

_{Ή-NMR (CDC1 3) δ} : 0.97 (9Η, s), 1. 7 (9H, s), 3.62 (1Η, brs), 5.81 (1H, brs), 6.90 (1H, brs), 6.92 (1H, d, J = 8Hz), 7.29 (1H, d, J = 6Hz), 7.38-7.53 (4H, m), 8.14 (lH, d, J = 8Hz)

Reference Example 9

N_t ert _butyl— 2- (4'-hydrazinophenyl) benzenesulfonamide hydrochloride (Compound 300)

N-tert-butyl-2- (4'-tert-butoxycarbonylhydrazinophenyl) Benzenesulfonamide (3 g) was dissolved in dichloromethane (15 Oml). 14.6% Dioxane hydrochloride 3 Om 1 was added, and the mixture was stirred at room temperature for 1 hour and further at 50 at 1 hour. The solvent was distilled off under reduced pressure. Ether dichloromethane in the residue

(5/1) and filtered. 2.17 g of the above compound was obtained.

Properties: colorless powder

Melting point: 1 13-1 15 ° C Ή-NMR (CDClj) δ: 1.03 (9H, s), 6.96 (2H, d, J = 8Hz), 7.27 (IH, dd, J = 8Hz, J = 2Hz), 7.33 (2H, d, J = 8Hz) ), 7.55 (1H, dd, J = 8Hz, J = 2Hz), 7.59 (1H, dd, J = 8Hz, J = 2Hz),

8.03 (lH, dd, J = 8Hz, J = 2Hz), 8.34 (1H, brs), 10.17 (2H, brs)

Example 33 (1)

2- (5-bromo-2-methylindole-3-ylthio) benzyl ester of nicotinic acid (Compound 301)

2-(2-oxopropyl) benzyl nicotinate 3 g! 2.24 g))-Bromophenylhydrazine hydrochloride was stirred for 3 hours under heating and reflux in tert-butyl alcohol 6 Om 1. The solvent was distilled off under reduced pressure. Dichloromethane 12 Om1 was added, and the mixture was washed with water 30 Om1. The organic layer was distilled off after drying. The residue was subjected to column chromatography (silica gel; dichloromethane). 3.9 g of the above compound was obtained.

Properties: pale yellow solid

Melting point: 143-145

_{Ή-NMR (CDC1 3) δ} : 2.40 (3Η, s), 5.46 (2Η, s), 6.99 (IH, dd, J = 7Hz, J = 2Hz), 7.07 (IH, d, J = 8Hz), 7.19 (IH, dd, J = 8Hz, J = 2Hz), 7.36-7.45 (4H, m),

7.54 (2H, dd, J = 7Hz, J = 2Hz), 8.26 (2H, dd, J = 8Hz, J = 2Hz), 8.46 (1H, brs)

Example 33 (2) One (6)

The following (Compound 302)-(Compound 306) were synthesized in the same manner as in Example 33 (1).

Example 33 (2)

6- (5-Bromo-2-methylindole-3-ylthio) benzyl ester of nicotinic acid (Compound 302)

Properties: yellow oil

_{Ή-NMR (CDC1 3) δ} : 2.50 (3H, s), 5.34 (2H, s), 6.68 (IH, dd, J = 8Hz, J = lHz),

7.22-7.46 (7H, m), 7.62 (IH, s), 7.95 (IH, dd, J = 8Hz, J = lHz), 8.51 (1H, s), 9.04 (lH, brs)

Example 33 (3)

2- (5- (2-N_tert-butylsulfamoylphenyl) —2-methylindole-3-ylthio) benzyl nicotinic acid ester (Compound 303) Properties: yellow powder

Melting point: 259-260

Ή-NMR (CDClj) (5: 0.84 (9H, s), 2.49 (3H, s), 3.61 (IH, s), 5.42 (2H, s), 6.97 (IH, dd, J = 8Hz, J = 5Hz) ), 7.31-7.42 (7H, m), 7.47-7.51 (4H, m),

8.11 (IH, dd, J = 7Hz, J = 2Hz), 8.22 (1H, dd, J = 8Hz, J = 2Hz),

8.28 (1H, dd, J = 5Hz, J = 2Hz), 8.45 (IH, brs)

Example 33 (4)

6- (5- (2-N-tert-butylsulfamoylphenyl) _2-methylindole-3-ylthio) Benzyl nicotinate (Compound 304) Properties: Yellow solid

Melting point: 90-92 ° C

_{Ή-NMR (CDC1 3) δ} : 0.90 (9H, s), 2.55 (3H, s), 3.54 (1H, s), 5.31 (2H, s),

6.78 (IH, dd, J = 7Hz, J = 2Hz), 7.27-7.54 (1 IH, m), 7.95 (IH, dd, J = 8Hz, J = 2Hz), 8.14 (1H, dd, J = 8Hz, J = 2Hz), 8.57 (1H, s), 9.01 (IH, d, J = 2Hz)

Example 33 (5)

4- (5- (2-N-tert-butylsulfamoylphenyl) -1-methylindole-3-ylthio) phenyloxyacetic acid tert-butyl monoester (Compound 305)

Properties: yellow oil

_{Ή-NMR (CDC1 3) δ} 0.85 (9Η, s), 1.46 (9Η, s), 2.54 (3H, s), 3.51 (IH, s), 4.42 (2H, s), 6.68 (2H, dd, J = 7Hz, J = 3Hz), 7.00 (2H, dd, J = 7Hz, J = 3Hz),

7.31-7.36 (2H, m), 7.40-7.46 (2H, m), 7.51 (IH, t, J = 7Hz), //: OSLOooaTI £ AV-

t i

(∞〇 ε) () H 969IHs ss.-

() 8f Ηί ¾lu =: 7.56 (1H, dd, J = 7Hz, J = 2Hz), 8.16 (IH, s), 8.18 (1H, dd, J = 8Hz, J = 2Hz),

8.25 (IH, dd, J = 8Hz, J = lHz), 8.48 (1H, dd, J = 8Hz, J = 2Hz),

9.19 (lH, dd, J = 7Hz, J = lHz), 9.18 (lH, s)

Example 34 (3)

4- (5— (2_N—tert—butylsulfamoylphenyl) —2-methylindole—3-ylsulfonyl) phenyloxyacetic acid tert—butylester (Compound 309)

Properties: yellow oil

Ή-NMR (CDC1 ₃ ) δ 0.94 (9Η, s), 1.47 (9H, s), 2.74 (3Η, s), 3.50 (IH, s),

4.52 (2H, s), 6.89 (2H, dd, J = 8Hz, J = 2Hz), 7.25 (1H, dd, J = 8Hz, J = 5Hz),

7.38 (2H, dd, J = 8Hz, J = 2Hz), 7.44 (IH, dd, J = 8Hz, J = 2Hz),

7.58 (IH, dd, J = 8Hz, J = 2Hz), 7.93 (2H, dt, J = 7Hz, J = 2Hz), 8.09 (IH, s),

8.18 (1H, dd, J = 8Hz, J = 2Hz), 8.91 (IH, brs)

Example 34 (4)

4- (5- (2-N-tert-butylsulfamoylphenyl) -1-2-methylindole-3-ylsulfonyl) benzyl benzoate (Compound 310)

Properties: reddish brown amorphous

_{Ή-NMR (CDC1 3) δ} : 0.94 (9Η, s), 2.76 (3H, s), 3.53 (IH, s), 7.23-7.28 (IH, m), 7.31-7.41 (7H, m), 7.47- 7.52 (IH, m), 7.58 (1H, t, J = 6Hz), 8.05 (2H, d, J = 8Hz), 8.10 (1H, s), 8.14 (2H, d, J = 8Hz), 8.19 (1H , D, J = 8Hz), 8.79 (1H, brs)

Example 35 (1) — (2)

(Compound 311) to (Compound 312) were synthesized in the same manner as in Example 22 (1). Example 35 (1)

2- (5- (2-Acetylphenyl) — 1— (3-dimethylamino-2-methylbenzoyl) -1-methylindole-3-ylsulfonyl) benzyl benzoate (Compound 31 1) Properties: brown amorphous

Ή-NMR (CDC1 ₃ ) δ: 1.87 (3, s), 2.28 (3H, s), 2.62 (3H, s), 2.72 (6H, s),

5.28 (2H, s), 7.03 (1H, d, J = 7Hz), 7.08 (IH, d, J = 2Hz), 7.20-7.40 (9H, m),

7.45-7.68 (5H, m), 7.97 (IH, s), 8.14 (IH, d, J = 8Hz)

Example 35 (2)

2- (1- (3-Dimethylamino-2-methylbenzyl) —2-methyl-5- (2-methylthiophenyl) indole — 3-ylsulfonyl) Benzyl benzoate (Compound 3 12)

Properties: yellow amorphous

Ή-NMR (CDC1 ₃ ) δ: 2.29 (3Η, s), 2.30 (3Η, s), 2.58 (3Η, s), 2.72 (6Η, s),

5.28 (2Η, s), 7.04 (lH, d, J = 8Hz), 7.13 (1Η, d, J = 9Hz), 7.15-7.29 (6H, m),

7.29-7.35 (4H, m), 7.38 (IH, d, J = 8Hz), 7.51-7.60 (3H, m), 8.06 (IH, s),

8.15 (lH, d, J = 8Hz)

Example 36 (1) — (7)

(Compound 313) to (Compound 319) were synthesized in the same manner as in Example 25 (1). Example 36 (1)

4- (1-(3-dimethylamino-2-methylbenzoyl) — 2-methyl_5_ (2-sulfamoylphenyl) indole — 3-ylsulfonyl) phenyloxyacetic acid (compound 313)

Properties: light brown powder

Melting point: 1 50— 1 53

'Η- 刚 R (DMS0-d ₆ ) δ: 2.18 (3Η, s), 2.57 (3H, s), 2.70 (6Η, s), 4.79 (2Η, s),

7.02-7.08 (2Η, m), 7.15-7.26 (3H, m), 7.31-7.37 (2H, m), 7.42 (IH, d, J = 8Hz),

7.58-7.67 (2H, m), 7.96 (2H, d, J = 8Hz), 8.07 (1H, d, J = 8Hz), 8.09 (1H, s)

Example 36 (2)

2- (1-(3-dimethylamino-2-methylbenzoyl) —2-methyl-5 (2-Sulfamoylphenyl) India 1- 3-^ r Rusulfonyl) Benzyl nicotinate (Compound 314)

Properties: yellow powder

Melting point: 117-120 ° C

_{Ή-NMR (CDC1 3) δ} : 2.33 (3H, s), 2.68 (3H, s), 2.84 (6H, s), 4.70 (IH, brs), 5.39 (2H, s), 7.11 (IH, d, J = 8Hz), 7.16 (IH, d, J = 7Hz), 7.21-7.25 (2H, m),

7.30-7.40 (5H, m), 7.43-7.46 (2H, m), 7.46-7.51 (2H, m), 7.55-7.60 (IH, m), 7.90 (lH, dd, J = 8Hz, J = 2Hz) , 8.16 (lH, d, J = 8Hz), 8.19 (1H, s),

8.63 (lH, dd, J = 4Hz, J = 2Hz)

Example 36 (3)

6- (1- (3-Dimethylamino-2-methylbenzoyl) -1-2-methyl-5- (2-sulfamoylphenyl) indole-3-3- ^ persulfonyl) benzyl nicotinate (Compound 315)

Properties: pale yellow powder

Melting point: 106-109 ° C

Ή-NMR (CDCI3) δ: 2.37 (3Η, s), 2.72 (3Η, s), 2.91 (6Η, s), 4.87 (2Η, brs),

5.40 (2Η, s), 7.06 (IH, d, J = 8Hz), 7.17 (1H, d, J = 7Hz),

7.22 (IH, dd, J = 8Hz, J = 2Hz), 7.30-7.42 (8H, m), 7.52 (IH, dt, J = 8Hz, J = 2Hz),

7.59 (lH, dt, J = 8Hz, J = 2Hz), 8.18 (1H, d, J = 7Hz), 8.28 (IH, d, J = 8Hz),

8.35 (1H, d, J = 2Hz), 8.55 (IH, dd, J = 8Hz, J = 3Hz), 9.21 (1H, d, J = 3Hz)

Example 36 (4)

4_ (11- (3-dimethylamino-2-methylbenzoyl) _ 2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) Benzyl benzoate (Compound 316)

Properties: yellow powder

Melting point: 1 17- 120 ° C Ή-NMR (CDCI3) δ: 2.29 (3H, s), 2.69 (3H, s), 2.74 (6H, s), 4.29 (2H, s),

5.37 (2H, s), 7.01 (IH, d, J = 7Hz), 7.09 (1H, d, J = 9Hz), 7.20-7.27 (1H, m),

7.31 (1H, d, J = 7Hz), 7.32-7.42 (7H, m), 7.50-7.56 (IH, m), 7.58-7.62 (IH, m),

8.08 (2H, d, J = 9Hz), 8.14-8.26 (3H, m), 8.27 (IH, d, J = lHz)

Example 36 (5)

1- (5-Dimethylamino-2-methylbenzoyl) -2-methyl-3- (2-pyridylsulfonyl) -1-5- (2-sulfamoylphenyl) indole (Compound 317)

Properties: yellow powder

Melting point: 122-125 ° C

'Η- 刚 R (CDC13) δ: 2.28 ( ₃ (, s), 2.76 (3Η, s), 2.96 (6H, s), 5.09 (2H, brs),

6.96 (1H, s), 7.01 (1H, d, J = 9Hz), 7.21 (2H, d, J = 8Hz), 7.32 (1H, d, J = 8Hz),

7.37 (IH, d, J = 8Hz), 7.46-7.52 (2H, m), 7.54-7.60 (IH, m), 7.91-7.99 (IH, m), 8.18 (1H, d, J = 8Hz), 8.22 (IH, d, J = 8Hz), 8.40 (1H, s), 8.64 (IH, d, J = 2Hz) Example 36 (6)

1- (3-Dibenzylamino-2-methylbenzoyl) -2-methyl-3- (2-pyridylsulfonyl) -5- (2-sulfamoylphenyl) indole (Compound 318)

Properties: yellow amorphous

_{Ή-NMR (CDC1 3) δ} : 2.41 (3Η, s), 2.63 (3Η, s), 4.11 (4H, s), 5.09 (2H, s),

6.96 (lH, d, J = 9Hz), 7.04 (lH, d, J = 7Hz), 7.10-7.17 ((2H, m), 7.17-7.30 (11H, m), 7.33 (IH, d, J = 7Hz ), 7.43-7.52 (2H, m), 7.58 (IH, dd, J = 7Hz, J = lHz), 7.90-7.97 (IH, m), 8.14-8.21 (2H, m), 8.40 (IH, d, J = lHz), 8.63 (1H, d, J = 5Hz)

Example 36 (7)

1- (5-dimethylamino-2-methoxybenzoyl) -1-methyl-3- (2-pyridylsulfonyl) -1-5- (2-sulfamoylphenyl) indole Compound 3 1 9)

Properties: yellow powder

Melting point: 1 84— 1 8 7 ° C

_{Ή-NMR (CDC1 3) δ} : 2.76 (3Η, s), 2.94 (6Η, s), 3.30 (3Η, s), 5.11 (2Η, s),

6.83 (1H, d, J = 9Hz), 6.94-7.00 (2H, m), 7.16 (2H, dd, J = 9Hz, 8Hz),

7.38 (1H, d, J = 8Hz), 7.44-7.52 (2H, m), 7.55-7.60 (1H, m), 7.95 (1H, t, J = 8Hz), 8.18 (1H, d, J = 8Hz) , 8.22 (1H, d, J = 8Hz), 8.40 (1H, s), 8.64 (1H, d, J = 5Hz) Example 37 (1) — (5)

In the same manner as in Example 27, the following (Compound 320) to (Compound 324) were synthesized.

Example 3 7 (1)

2-(1-(3-Dimethylamino-2-methylbenzoyl) — 2-methyl _ 5 _ (2-sulfamoylphenyl) indole-3-ylsulfonyl) nicotinic acid (Compound 320)

Properties: pale yellow powder

Melting point: 240 (dec.)

'H-NMR (DMS0-d ₆ ) 6: 2.17 (3H, s), 2.57 (3H, s), 2.66 (6H, s),

7.06 (1H, d, J = 4Hz), 7.15 (1H, s), 7.17 (1H, d, J = 8Hz), 7.28 (2H, d, J = 7Hz),

7.31-7.40 (2H, m), 7.53-7.62 (2H, m), 7.74 (1H, dd, J = 6Hz, 5Hz), 7.97 (1H, s),

8.03 (1H, d, J = 8Hz), 8.15 (1H, d, J = 8Hz), 8.69 (1H, dd, J = 4Hz, 2Hz)

Example 3 7 (2)

6- (1-(3-dimethylamino-2-methylbenzoyl) _ 2 _methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) nicotinic acid (compound 3 2 1)

Properties: pale yellow powder

Melting point: 1 6 8—17 2 ° C Ή-NMR (D S0-d ₆ ) δ: 2.19 (3H, s), 2.62 (3H, s), 2.68 (6H, s),

7.09 (IH, d, J = 9Hz), 7.14-7.20 (3H, m), 7.24 (IH, d, J = 9Hz), 7.30-7.38 (2H, m),

7.41 ((IH, d, J = 8Hz), 7.58-7.66 (2H, m), 8.02 (1H, s), 8.05 (IH, d, J-9Hz),

8.34 (1H, d, J = 8Hz), 8.51 (1H, dd, J = 8Hz, J-2Hz), 9.10 (1H, s)

Example 37 (3)

4- (1-(3-Dimethylamino-2-methylbenzoyl) — 2-methyl_5— (2 _sulfamoylphenyl) indole—3-ylsulfonyl) benzoic acid (Compound 322)

Properties: pale yellow powder

Melting point: 162-165 ° C

_{Ή-NMR (CDC1 3) δ} : 2.29 (3Η, s), 2.70 (3H, s), 2.73 (6H, s), 4.43 (2Η, brs), 7.00 (1Η, d, J = 8Hz), 7.11 ( IH, d, J = 9Hz), 7.20-7.28 (2H, m), 7.29 (IH, d, J = 8Hz), 7.36 (IH, d, J = 7Hz), 7.53 (IH, t, J = 8Hz) , 7.62 (1H, t, J = 8Hz), 8.12 (2H, d, J = 8Hz), 8.15-8.21 (3H, m), 8.29 (IH, s)

Example 37 (4)

2- (5- (2-Acetylphenyl) — 1— (3-Dimethylamino-2-methylbenzoyl) -1-Methylindole-3-ylsulfonyl) benzoic acid (compound

323)

Properties: pale yellow powder

Melting point: 129-132 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.03 (3Η, s), 2.15 (3Η, s), 2.56 (3Η, s), 2.65 (6Η, s), 7.08-7.17 (3Η, m), 7.31 -7.40 (3Η, m), 7.48-7.50 (IH, m), 7.55-7.61 (2Η, m), 7.61-7.67 (IH, m), 7.67-7.78 (3Η, m), 8.08 (IH, d, (J = 8Hz)

Example 37 (5)

2- (1- (3-dimethylamino-2-methylbenzoyl) _ 2-methyl-5- (2-methylsulfonylphenyl) indole-3-ylsulfonyl) benzoic acid (Compound 324)

Properties: yellow powder

Melting point: 154-158 ° C

_{'HN R (DMSO-d 6} ) 6: 2.15 (3H, m), 2.55 (3H, s), 2.64 (3Η, s), 2.71 (3Η, s), 7.12 (IH, d, J = 9Hz), 7.17 (1H, d, J = 7 Hz), 7.22 (IH, d, J = 10 Hz),

7.30-7.40 (3H, m), 7.60-7.78 (5H, m), 7.87 (IH, s), 8.10 (2H, t, J = 8Hz) Example 38 (1)

1- (3_Benzylamino-1-methylbenzoyl) -2-methyl-3- (2-pyridylsulfonyl) _5— (2-sulfamoylphenyl) indole (Compound 325)

1- (3-Dibenzylamino-2-methylbenzoyl) 1-2-Methyl-3_ (2_pyridylsulfonyl) -1 5- (2-Sulfamoylphenyl) Indole 9 Omg is dissolved in methanol 6m1 and ethyl acetate 4m1 and water 9 Omg of palladium oxide on carbon was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 15 hours and at 50 at 1 day. The catalyst was filtered off and concentrated, and the residue was subjected to silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain 15 mg of the above compound.

Properties: colorless powder

Melting point: 148 _ 152

_{Ή-NMR (CDC1 3) δ} : 2.18 (3Η, s), 2.72 (3H, s), 4.17 (lH, brs),

4.40 (2H, d, J = 5Hz), 5.10 (2H, s), 6.70 (IH, d, J = 8Hz), 6.84 (1H, d, J = 8Hz)

7.12-7.18 (2H, m), 7.22 (IH, dd, J = 9Hz, J = 2Hz), 7.30-7.35 (1H, m),

7.35-7.40 (5H, m), 7.45-7.54 (2H, m), 7.54-7.60 (IH, m), 7.91-7.96 (IH, m),

8.20 (2H, dd, J = 9Hz, J = 8Hz), 8.42 (IH, s), 8.66 (IH, d, J = 5Hz)

Example 38 (2)

The following (Compound 326) was synthesized in the same manner as in Example 38 (1).

1- (3-amino-2-methylbenzoyl) 1- 2-methyl-3- (2-pyridyl Sulfonyl) — 5— (2-Sulfamoylphenyl) Indole (Compound 326)

Properties: light brown powder

Melting point: 1 39—143 ° C

Ή-NMR (CDC1 ₃ ) δ 2.17 (3Η, s), 2.72 (3Η, s), 5.12 (2H, s), 6.76 (IH, d, J = 8Hz),

6.92 (IH, d, J = 8Hz), 7.10 (IH, t, J = 8Hz), 7.16 (1H, d, J = 9Hz),

7.21 (IH, dd, J = 8Hz, J = 2Hz), 7.37 (IH, dd, J = 8Hz, 1Hz), 7.45-7.51 (2H, m),

7.56-7.60 (1H, m), 7.95 (IH, dt, J = 8Hz, J = 2Hz), 8.14-8.21 (2H, m), 8.42 (IH, s),

8.65 (lH, d, J = 4Hz)

Example 39

2- (1-(3-Dimethylamino-2-methylbenzoyl) -1-2-methyl-5- (2-methylsulfonylphenyl) indole-3-ylsulfonyl) benzyl benzoate (Compound 327)

0.25 g of 2- (1- (3-dimethylamino-2-methylbenzoyl) -2-methyl-5- (2-methylthiophenyl) indole-3-ylsulfonyl) benzyl benzoate was dissolved in 4 ml of salt dimethylene, 36 g of mCPBAO was added and the mixture was stirred at room temperature for 2 hours. The reaction solution was washed with an aqueous sodium thiosulfate solution and an aqueous sodium hydrogen carbonate solution. After drying over anhydrous magnesium sulfate, the mixture was concentrated. The residue was subjected to silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain 84 mg of the above compound.

Properties: yellow powder

Melting point: 106—1 10

_{'H-NMR (CDC1 3)} 6 2.29 (3H, s), 2.58 (3H, s), 2.60 (3H, s), 2.72 (6Η, s),

5.23 (2H, s), 7.03 (IH, d, J = 8Hz), 7.11 (1H, d, J = 9Hz), 7.20-7.38 (9H, m),

7.52-7.65 (5H, m), 8.04 (IH, s), 8.12 (IH, d, J = 5Hz), 8.21 (IH, d, J = 7Hz) Example 40 (1) — (3) The following (Compound 328) — (Compound 330) was synthesized in the same manner as in Example 29 (1).

Example 40 (1)

5-Dimethylamino-2-methoxybenzoic acid (Compound 328)

Properties: yellow powder

Melting point: 84-86 ° C

_{Ή-NMR (CDC1 3) δ} : 2.94 (6Η, s), 4.01 (3H, s), 6.91-6.98 (2Η, m),

7.54 (lH, d, J = 4Hz)

Example 40 (2)

5 _Dimethylamino-2-methylbenzoic acid (Compound 329)

Properties: yellow powder

Melting point: 1 29— 1321:

'H-NMR (DMSO-d ₆ ) δ: 2.38 (3Η, s), 2.87 (6Η, s), 6.84 (IH, dd, J = 8Hz, J = 3Hz), 7.09 (IH, d, J = 8Hz) ), 7.14 (1H, d, J = 3Hz)

Example 40 (3)

3-Dibenzylamino-2-methylbenzoic acid (Compound 330)

Properties: colorless powder

Melting point: 1 57- 160 ° C

'H-NMR (DMS0-d ₆ ) δ: 2.58 (3Η, s), 4.06 (4Η, s), 7.09 (lH, t, J = 8Hz),

7.17-7.22 (3H, m), 7.22-7.30 (8H, m), 7.37 (IH, d, J = 8Hz)

Example 41 (1)-(2)

The following (Compound 331) to (Compound 332) were obtained in the same manner as in Example 16 (1).

Example 41 (1)

2- (5-Bromo-2-methylindole-3-ylsulfonyl) methyl benzoate (Compound 331) Properties: colorless powder

Melting point: 1 85— 186.5 ° C

Ή-NMR (DMS0-d ₆ ) <5: 2.67 (3H, s), 3.81 (3H, s), 7.32 (lH, dd, J = 8Hz, J-2Hz), 7.39 (IH, d, J = 8Hz) ), 7.58 (IH, dd, J = 8Hz, J = 2Hz), 7.65-7.72 (2H, m),

7.85 (1H, d, J = 2Hz), 7.90 (IH, dd, J = 8Hz, J = 2Hz), 12.44 (IH, brs)

Example 41 (2)

2-tert-butyl 2- (5-bromo-2-methylindole-3-ylsulfonyl) benzoate (Compound 332)

Properties: colorless powder

Melting point: 278 (d e c.)

Ή-NMR (DMSO- d ₆ ) δ: 1.57 (9H, s), 2.63 (3H, s), 7.28-7.32 (1H, m),

7.37 (IH, d, J = 8Hz), 7.53 (1H, d, J = 7Hz), 7.61-7.69 (2H, m), 7.82-7.86 (2H, m) Example 42 (1) — (3)

The following (Compound 333) — (Compound 335) were obtained in the same manner as in Example 18 (1).

Example 42 (1)

2- (5-bromo-11- (3-dibenzylamino-2-methylbenzoyl) -2-methylindole-3-ylsulfonyl) benzyl benzoate (Compound 333) Properties: brown amorphous

_{Ή-NMR (CDC1 3) δ} : 2.35 (3Η, s), 2.48 (3H, s), 4.08 (4H, s), 5.27 (2H, s),

6.77 (IH, d, J = 9Hz), 6.98 (IH, d, J = 7Hz), 7.10-7.16 (2H, m), 7.16-7.30 (1 IH, m),

7.30-7.40 (5H, m), 7.52-7.60 (3H, m), 8.02-8 · 10 (IH, m), 8.14 (1H, d, J = 3Hz) Example 42 (2)

2- (5-Promo- 11- (3-dimethylamino-2-methylbenzoyl) -12-Methylindole-13-ylsulfonyl) tert-butyl benzoate (Compound 334) Properties: yellow amorphous

'.Eta. negation _{R (CDC1 3) δ: 1.60} (9H, s), 2.24 (3H, s), 2.58 (3H, s), 2.71 (6H, s),

6.92-7.00 (2H, m), 7.20-7.28 (3H, m), 7.52-7.60 (3H, m), 8.02 (1H, d, J = 8Hz), 8.14 (lH, d, J = 2Hz)

Example 42 (3)

2- (5-bromo-1- (3-dimethylamino-2-methylbenzoyl) -2-methylindole-3-ylsulfonyl) methyl benzoate (Compound 335)

Properties: yellow amorphous

_{Ή-NMR (CDC1 3) δ} : 2.24 (3Η, s), 2.55 (3H, s), 2.70 (6Η, s), 3.85 (3Η, s),

6.94 (1Η, d, J = 9Hz), 6.98 (1Η, dd, J = 7Hz, J = 2Hz,), 7.21-7.28 (3H, m),

7.57-7.6 (3H, m), 8.07 (IH, dd, J = 7Hz, J = 3Hz), 8.17 (1H, d, J = 7Hz)

Example 43 (1)-(5)

The following (Compound 336) — (Compound 340) were obtained in the same manner as in Example 22 (1).

Example 43 (1)

2- (5- (2-N-tert-butylsulfamoylphenyl) — 1- (3-dibenzylamino-2-methylpentyl) -2-methylindole-3-ylsulfonyl) Benzyl benzoate (Compound 336 )

Properties: yellow amorphous

_{Ή-NMR (CDC 1 3)} δ: 0.92 (9Η, s), 2.40 (3H, s), 2.48 (3Η, s), 3.77 (IH, s),

4.11 (4H, s), 5.19 (2H, s), 6.96-7.06 (2H, m), 7.06-7.12 (2H, m),

7.16-7.30 (10H, m), 7.30-7.38 (6H, m), 7.46-7.60 (6H, m), 8.10 (1H, s),

8.12-8.21 (2H, m)

Example 43 (2)

2- (5- (3-Acetylphenyl) — 1— (3-Dimethylamino-2-methyl Benzyl) -2-methylindole-3-ylsulfonyl) benzyl benzoate (Compound 337)

Properties: yellow amorphous

_{Ή-NMR (CDC1 3) δ} : 2.20 (3Η, s), 2.64 (3H, s), 2.65 (3H, s), 2.73 (6H, s), 5.29 (2H, s), 7.03 (IH, d, J = 7Hz), 7.13 (1H, d, J = 9Hz), 7.20-7.34 (5H, m), 7.34-7.40 (3H, m), 7.51 (IH, d, J = 8Hz), 7.56-7.62 (3H , M), 7.78 (IH, d, J = 9Hz), 7.91 (IH, d, J = 8Hz) Example 43 (3)

2- (5- (2_N_tert-butylsulfamoylphenyl) _ 1 _ (3-dimethylamino-2-methylbenzoyl) 1-2-methylindole-3-ylsulfonyl) Benzyl benzoate (Compound 338)

Properties: colorless powder

Melting point: 152-154

_{Ή-NMR (CDC1 3) δ} : 0.94 (9Η, s), 2.27 (3H, s), 2.55 (3H, s), 2.72 (6H, s), 3.76 (IH, s), 5.23 (2H, s) , 6.99 (IH, d, J = 8 Hz), 7.13 (IH, d, J = 9 Hz), 7.22 (IH, t, J = 8 Hz),

7.27-7.39 (8H, m), 7.48 (IH, t, J = 8Hz), 7.50-7.61 (4H, m), 8.12 (IH, s),

8.13-8. 0 (2H, m)

Example 43 (4)

2- (5- (3-Acetylphenyl) — 1— (3-Dimethylamino-2-methylbenzoyl) _ 2-Methylindole-3-ylsulfonyl) tert-butyl benzoate (Compound 339)

Properties: yellow amorphous

_{'H-NMR (CDC1 3)} δ: 1.58 (9H, s), 2.29 (3H, s), 2.66 (3H, s), 2.67 (3H, s), 2.73 (6H, s), 7.05 (IH, d , J = 8Hz), 7.15 (IH, d, J = 9Hz), 7.20-7.30 (IH, m), 7.39 (IH, d, J = 8Hz), 7.52 (1H, t, J = 8Hz), 7.53- 7.60 (4H, m), 7.79 (IH, d, J = 8Hz), 7.92 (IH, d, J = 8Hz), 8.04-8.09 (lH, m), 8.12 (lH, s), 8.18 (1H, s )

Example 43 (5) 2- (5- (2-acetylphenyl) 1-1_ (3-dimethylamino-2-methylbenzoyl) _2-methylindole-3-ylsulfonyl) methyl benzoate (Compound 340)

Properties: light green amorphous

_{Ή-NMR (CDC1 3) δ} : 1.90 (3Η, s), 2.29 (3Η, s), 2.63 (3Η, s), 2.69 (6Η, s), 3.84 (3Η, s), 7.05 (IH, dd, J = 8Hz, J = lHz), 7.08 (IH, d, J = lHz,), 7.23-7.29 (2H, m), 7.37-7.43 (2H, m), 7.48-7.68 (6H, m), 7.97 ( 1H, s), 8.12 (1H, dd, J = 8Hz, J = 2Hz) Example 44 (1)-(1 4)

The following (Compound 341) — (Compound 354) was obtained in the same manner as in Example 25 (1).

Example 44 (1)

2- (1- (2,6-dimethylbenzoyl) —2-methyl-5- (2-sulfamoylphenyl) indole—3_ylsulfonyl) benzyl benzoate (compound 34 1)

Properties: colorless oil

_{Ή-NMR (CDC1 3) δ} : 2.12 (6H, s), 2.45 (3H, s), 4.61 (2H, s), 5.05 (2H, s),

7.09-7.14 (2H, m), 7.28-7.36 (8H, m), 7.49-7.67 (6H, m), 8.11-8.24 (3H, m) Example 44 (2)

2- (1- (2,4-Dimethoxybenzoyl) —2_methyl_5_ (2-sulfamoylphenyl) indole—3_ylsulfonyl) benzyl benzoate (Compound 342)

Properties: colorless oil

_{'H-NMR (CDC1 3)} δ: 2.60 (3Η, s), 3.45 (3Η, s), 4.50 (2Η, s), 5.10 (2H, s),

6.89 (3H, s), 6.40 (IH, d, J = 2Hz), 6.56-6.60 (IH, m), 7.12 (1H, d, J = 9Hz),

7.20-7.36 (7H, m), 7.45-7.62 (6H, m), 8.08 (1H, s), 8.15 (2H, d, J = 7Hz)

Example 44 (3) 2- (1- (2-benzylbenzoyl) -1-2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzyl benzoate (compound 343)

Properties: colorless powder

Melting point: 107-109T:

_{'H-NMR (CDC1 3)} δ: 2.15 (3H, s), 4.10 (2H, s), 4.58 (2H, s), 5.03 (2H, s),

6.94 (1H, d, J = 9Hz), 7.02 (2H, d, J = 7Hz), 7.06-7.18 (3H, m), 7.21 (IH, d, J = 9Hz),

7.26-7.35 (7H, m), 7.39 (IH, d, J = 8Hz), 7.48-7.66 (7H, m), 8.11 (1H, s),

8.13—8.20 (2H, m)

Example 44 (4)

2- (1-(6-Dimethylaminonicotinol) -1-2-methyl _5_ (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzylester benzoate (Compound 344)

Properties: pale yellow oil

_{Ή-NMR (CDC1 3) δ} : 2.69 (3Η, s), 3.21 (6H, s), 4.57 (2Η, brs), 5.08 (2Η, s),

6.48 (IH, d, J = 8Hz), 7.17 (1H, d, J = 8Hz), 7.26-7.41 (9H, m), 7.47-7.65 (3H, m),

7.76 (IH, dd, J = 8Hz, J = 3Hz), 8.10 (IH, d, J = 2Hz), 8.15 (1H, d, J = 8Hz),

8.19 (1H, d, J = 8Hz), 8.51 (IH, d, J = 2Hz)

Example 44 (5)

2- (1- (2-furoyl) -1-2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) Benzoic acid benzyl ester (Compound 345)

Properties: colorless oil

_{Ή-NMR (CDC1 3) δ} : 2.58 (3Η, s), 4.59 (2Η, s), 5.07 (2Η, s), 6.66 (IH, d, J = 2Hz), 7.19 (1H, d, J = 8Hz ), 7.26-7.38 (8H, m), 7.49-7.68 (6H, m), 8.11 (1H, d, J = 2Hz), 8.17 (lH, dd, J = 8Hz, J = 2Hz), 8.21 (IH, (dd, J = 8Hz, J = 2Hz)

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'(s ΉΖ) 90 -S' (s-iq S9 '' (s ¾) S 'l-9 ( ^ε 13α3) HWN-H,

: ^ '

(8 ε 呦 ^ »^: e Kku ^ 鏹 violent, S '^ (1Γ" ^ Γ ^ Ο- ε -Λ (-(ί ~ ^^ (^^^ (-Ζ)--(^-Ζ -(/ 、く ^ 口乙ー)-I)-Z

(8)

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(i) Ρ

'(= i' ΖΗ8 = ί 'ΡΡ' I · 8 '(s ΉΙ) LO · 8' (ω Ή3) 29 -8 ^ Ί '(' Η8) 'L' (s

'ζ ί'PP'HOSI · 9 '(s ΉΖ) Ζ0' 9 '(s ¾)' (s ^l HS) AO '(s Ήδ) 09' Ζ: Q ( ^ε 1303) ΗΚΝ-Η, 呦 ^^ W: ¥ tc¾

(9 ε

ε (

-Z) -9-(d ^-s _ — mouth. "^^ one Ό-τ -Λ (^-Ζ)-ζ

06S.0 / 00df / X3d U9 / 10 OAV Example 44 (9)

2- (2-Methyl-5- (2-sulfamoylphenyl) -111- (2-tenol) indole-3-ylsulfonyl) benzyl benzoate (Compound 349)

Properties: pale yellow oil

Ή-NMR (CDC1 ₃ ) δ 2.60 (3Η, s), 4.63 (2Η, s), 5.08 (2H, s),

7.13 (lH, dd, J = 5Hz, J = 4Hz), 7.26-7.34 (8H, m), 7.49-7.65 (6H, m),

7.87 (IH, d, J = 5Hz), 8.11 (IH, d, J = 2Hz), 8.15 (1H, dd, J = 8Hz, J = 2Hz),

8.22 (lH, dd, J = 8Hz, J = 2Hz)

Example 44 (10)

2- (2-Methyl-1_ (2-Methyl-3-furoyl) -1-5_ (2-Sulfamoylphenyl) Indian 1-Ruth 3-ylsulfonyl) Benzoic acid benzyl ester (Compound 350)

Properties: pale yellow oil

_{Ή-NMR (CDC1 3) δ} : 2.50 (3Η, s), 2.62 (3Η, s), 4.61 (2H, brs), 5.08 (2H, s),

6.33 (IH, d, J = 2Hz), 7.23-7.37 (9H, m), 7.45-7.70 (5H, m), 8.08 (IH, d, J = 2Hz), 8.13 (IH, dd, J = 7Hz, J = 2Hz), 8.21 (IH, dd, J = 7Hz, J = 2Hz)

Example 44 (11)

2- (2-Methyl_1- (2-Methylbenzoyl) — 5 -— (2-Sulfamoylphenyl) India-One 3-ylsulfonyl) Benzylester Benzoate (Compound 351)

Properties: pale yellow oil

_{Ή-NMR (CDC1 3) δ} : 2.40 (3Η, s), 2.50 (3Η, s), 4.59 (2H, s), 5.05 (2Η, s),

7.02 (IH, d, J = 9.0Hz), 7.18-7.33 (8H, m), 7.45-7.64 (7H, m), 8.16 (2H, m),

8.23 (lH, d, J = 8Hz)

Example 44 (12) 2- (1- (3-chloro-2-benzoyl) —2-methyl-5- (2-sulfamoylphenyl) indole-3-sillsulfonyl) benzylester benzoate (Compound 352)

Properties: colorless solid

Melting point: 92-94 ° C

Ή-NMR (CDC1 ₃ ) 5: 2.41 (3H, s), 2.48 (3H, s), 4.82 (2Η, s), 5.22 (2Η, s),

7.18-7.38 (10Η, m), 7.48-7.85 (6H, m), 8.16 (1H, d, J = 8Hz), 8.23 (IH, d, J = 4Hz), 8.24 (lH, d, J = 3Hz) '

Example 44 (13)

2-(1-(4-Methoxybenzoyl) — 2-methyl _5_ (2-sulfamoylphenyl) Indole — 3-ylsulfonyl) Benzoic acid benzyl ester (353)

Properties: pale yellow oil

Ή-NMR (CDC1 ₃ ) δ: 2.62 (3Η, s), 3.92 (3H, s), 4.62 (2H, s), 5.2 (2H, s),

6.95 (2H, d, J = 8Hz), 7.11 (IH, d, J = 2Hz), 7.30-7.75 (14H, m), 8.13 (1H, d, J = 2Hz), 8.16 (lH, d, J = 9Hz), 8.21 (lH, d, J = 5Hz)

Example 44 (14)

2- [1- (2,3-Dimethylbenzoyl) -2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl] benzyl benzoate (Compound 354)

Properties: colorless oil

_{Ή-NMR (CDC1 3) δ} : 2.28 (3Η, s), 2.37 (3H, s), 2.49 (3Η, s), 4.58 (2Η, brs), 5.04 (2H, s), 7.06-7.16 (3H, m), 7.24-7.34 (7H, m), 7.38 (IH, d, J = 8Hz),

7.52 (IH, dd, J = 8Hz, J = 2Hz), 7.56-7.65 (4H, m), 8.13 (1H, d, J = 2Hz),

8.15 (1H, dd, J = 7Hz, J = 2Hz), 8.22 (IH, dd, J = 7Hz, J = 2Hz)

Example 45 (1)-(2) (s ε 呦邈 violent, {Λ (^ Λ (Λ (-£ -Λ (-ύ y (Nye

YZ)-S-(^ -Ζ-(Λ (^ ^ (^^-ζ-^-I)-z

¾ (τ ζ ε one (s o) stop w '^ m ^ (D L Z \

(ZH8 = f 'P'Hl) 8f 8'(s'Hl)90'8'(in Ή8) Z6 -A-98 Ί' (ω 'HI) 08ί ί' (Ήε) U (m 'Η9) -0' L '(s' Η9) LQ · ε' (s ΉΟ 39 T (s Ήε) 'I' (s Ήε) 52: P ( ^£ I3a3) ¾WN-H,

(9 s ε

-)-Τ-((~ ^^ Λ (Ά-£) -S) -Z

(ZH9 = f 'P ΉΙ) 1Γ8' (ZH9 = f 'P' HI) 91 · 8 '(s' HI) 11 · 8 '(in Ή9) Z9ΖΖ-9 ^ ίί (in Ή9Ι)' L '(ZH8 = f ΉΖ ΉΖ) WL' (ZH6 = f 'ΉΖ) 96' 9 '(s Ή2) SO' S '(s' H 8S' (s' m 80 '' (s Ή2) '(s 'HS) 8S: έ> (' ΙΟΟΟ) ¾WN-H,

^:: Violent '^ {Λ (~ ^ (Λ (-£ -Λ (-Λ <

S -Λ (^-Ζ-{Λ (/, ^^-i ^-Ζ-^ (^ ^ -ί)-I)-ζ

(O S ^ m

¾ (9 s εί # ^ »one (s s ει¾ ^» 丄 '^ m ^ (τ) 9 z

06S.0 / 00df / X3d U9 / 10 OAV Properties: colorless powder

Melting point: 174—177

Ή-NMR (DMS0-d ₆ ) δ: 2.10 (3Η, s), 2.56 (3H, s), 6.99-7.04 (IH, m),

7.04-7.12 (2H, m), 7.18 (2H, s), 7.25 (2H, d, J = 7Hz), 7.54-7.68 (3H, m),

7.68-7.76 (IH, m), 7.88 (IH, s), 8.05 (IH, d, J = 8Hz), 8.13 (1H, d, J = 8Hz)

Example 46 (2)

2- (1- (2,6-dimethylpentyl) -1-2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid (compound 358) Properties: colorless powder

Melting point: 156-159 ° C

_{Ή-NMR (CDC1 3) δ} : 2.15 (6H, s), 2.29 (3H, s), 5.41 (2H, s), 7.06-7.13 (4H, m),

7.30-7.35 (2H, m), 7.53 (IH, t, J = 8Hz), 7.56-7.70 (4H, m), 8.16 (IH, d, J = 8Hz),

8.36 (lH, d, J = 7Hz), 8.41 (lH, s)

Example 46 (3)

2- (5-(2-N-tert-butylsulfamoylphenyl) — 1- (3-dimethylamino-2-methylpentyl) -2-methylindole-3-ylsulfonyl) benzoic acid (Compound 359)

Properties: colorless powder

Melting point: 140—143 ° C

Ή-NMR (CDCI3) δ: 1.01 (9Η, s), 2.20 (3Η, s), 2.35 (3Η, s), 2.67 (6H, s), 5.70 (IH, s), 7.00 (1H, d, J) = 8Hz), 7.06 (IH, d, J = 8Hz), 7.15-7.30 (4H, m), 7.50 (IH, t, J = 7Hz), 7.52-7.60 (2H, m), 7.60-7.65 (2H, m), 8.21 (IH, d, J = 7 Hz), 8.31 (IH, d, J = 9 Hz), 8.51 (lH, s),

Example 46 (4)

2- (1- (3-dimethylamino-2-methylbenzoyl) -1-5- (3- (1-hydroxyethyl) phenyl) -2-methylindole-3-ylsulfonyl) Benzoic acid (Compound 360)

Properties: yellow powder

Melting point: 135-138V

'H-NMR (DMSO-d ₆ ) δ: 1.37 (3Η, d, J = 7 Hz), 2.17 (3H, s), 2.57 (3H, s), 2.65 (6H, s), 4.80 (IH, q, J = 7Hz), 7.05-7.14 (2H, m), 7.30-7.35 (IH, m), 7.35-7.41 (2H, m), 7.41-7.50 (2H, m), 7.53 (1H, s), 7.67 ( 1H, s), 7.70-7.78 (2H, m), 8.01 (IH, s), 8.18-8.21 (IH, m)

Example 46 (5)

2- (1- (2,4-dimethoxybenzoyl) _2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid (Compound 361)

Properties: colorless powder

Melting point: 164 _ 167

_{'H-NMR (CDC1 3)} δ: 2.41 (3Η, s), 3.46 (3H, s), 3.88 (3H, s), 5.25 (3H, s), 6.39 (IH, s),

6.60 (IH, d, J = 9Hz), 7.10 (IH, d, J = 9Hz), 7.23 (IH, d, J = 8Hz), 7.35 (IH, d, J = 8Hz),

7.46-7.5 (1H, m), 7.54-7.70 (5H, m), 8.14 (1H, d, J = 9Hz), 8.35 (2H, s)

Example 46 (6)

2- (1-(2-Benzylbenzoyl) -2-methyl-5- (2-sulfamoyl phenyl) Indole-3-ylsulfonyl) Benzoic acid (Compound 362) Properties: colorless powder

Melting point: 145-148 ° C

Ή-NMR (DMS0-d ₆ ) 6: 2.27 (3H, s), 4.08 (2H, s), 6.90 (1H, d, J = 9 Hz),

7.03 (2H, d, J = 8Hz), 7.08-7.12 (1H, m), 7.12-7.20 (4H, m), 7.28 (IH, d, J = 6Hz), 7.42 (1H, t, J = 8Hz) , 7.48-7.53 (2H, m), 7.58-7.69 (4H, m), 7.75 (IH, t, J = 7Hz), 7.92 (1H, s), 8.05 (IH, d, J = 7Hz), 8.11 ( (1H, d, J = 7Hz)

Example 46 (7) 2- (1- (6-Dimethylaminonicotinol) — 2-Methyl_5- (2-Sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid (Compound 363)

Properties: light red amorphous

Ή-NMR (DMS0-d ₆ ) δ 2.68 (3H, s), 3.07 (3Η, s), 3.10 (3Η, s), 7.06 (2Η, s), 7.23 (IH, dd, J = 7 Hz, J = 2Hz), 7.31 (1H, d, J = 7Hz), 7.39 (IH, d, J = 8Hz),

7.50-7.65 (5H, m), 7.81 (IH, s), 8.05 (2H, dd, J = 8Hz, J = 6Hz), 9.33 (IH, brs) Example 46 (8)

2- (1— (2-furoyl) —2-methyl—5— (2-sulfamoylphenyl) indole—3-ylsulfonyl) benzoic acid (compound 364)

Properties: pale yellow powder

Melting point: 1 73— 175

Ή-NMR (DMS0-d ₆ ) δ 2.66 (3Η, s), 6.93 (IH, s), 7.21-7.31 (4H, m),

7.60-7.74 (5H, m), 7.90 (IH, s), 8.06 (IH, d, J = 7Hz), 8.17 (IH, d, J = 7Hz), 8.26 (1H, s)

Example 46 (9)

2- (2_Methyl_1- (1-Methylpyrroyl-2- 2-caprolponyl) -1-5- (2-Sulfamoylphenyl) Indole-3-ylsulfonyl) Benzoic acid (Compound

365)

Properties: colorless powder

Melting point: 1 70 _ 1 72

Ή-NMR (DMS0-d ₆ ) δ 2.42 (3Η, s), 4.06 (3Η, s), 5.25 (2Η, brs), 6.17 (1H, s),

6.60 (IH, s), 7.07 (IH, s), 7.14 (1H, d, J = 8Hz), 7.32 (IH, d, J = 9Hz),

7.36 (IH, d, J = 8Hz), 7.51-7.65 (5H, m), 8.15 (IH, d, J = 8Hz), 8.33 (IH, s),

8.35 (lH, d, J = 8Hz)

Example 46 (10) 2- (2-Methyl-1- (1-methylindole-2-carbonyl) -5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid

366)

Properties: colorless powder

Melting point: 178-18 o

Ή-NMR (CDClj) δ: 2.45 (3Η, s), 4.14 (3Η, s), 5.28 (2H, brs), 6.97 (IH, s), 7.12 (IH, dd, J = 8Hz, J = 2Hz) , 7.20 (IH, dd, J = 8Hz, J = 6Hz), 7.33 (IH, d, J = 8Hz),

7.37 (1H, d, J = 8Hz), 7.45-7.53 (3H, m), 7.58-7.69 (5H, m), 8.15 (1H, d, J = 8Hz),

8.37 (IH, dd, J = 8Hz, J = 2Hz), 8.39 (IH, s)

Example 46 (1 1)

2- (11- (4-fluorobenzoyl) -2-methyl-5- (2-sulfamoyl phenyl) indole-3-ylsulfonyl) benzoic acid (Compound 367) Properties: colorless powder

Melting point: 169-171 ° C

Ή-NMR (CDCI3) δ: 2.54 (3Η, s), 4.68 (2Η, brs), 5.07 (2H, s),

7.05 (1H, dd, J = 7Hz, J = 2Hz), 7.17 (1H, dd, J = 8Hz, J = 2Hz),

7.19 (IH, dd, J = 8Hz, J = 2Hz), 7.25-7.34 (7H, m), 7.49-7.67 (5H, m),

7.77 (IH, dd, J = 8Hz, J = 2Hz), 7.79 (1H, dd, J = 8Hz, J = 2Hz), 8.12 (1H, d, J = lHz), 8.15 (IH, dd, J = 8Hz) , J = lHz), 8.24 (IH, dd, J = 8Hz, J = 2Hz)

Example 46 (12)

2- (2-methyl-1- (2-methylbenzoyl) -1-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid (compound 368) Properties: colorless powder

Melting point: 163-166

_{Ή-NMR (CDC1 3) δ} : 2.40 (3Η, s), 2.50 (3H, s), 4.56 (2H, s), 7.02 (. IH, d, J = 9 OHz), 7.18-7.33 (4H, m ), 7.45-7.64 (3H, m), 8.15 (1H, dd, J = 7Hz, J = 2Hz), 8.16 (1H, dd, J = 7Hz, J = 2Hz), 8.23 (1H, d, J = 8Hz)

Example 46 (1 3)

2- (2-methyl-1- (2-methyl-3-furoyl) _ 5 _ (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid (compound 369) Properties: colorless powder

Melting point: 1 3 9—1 4 1 ° C

_{Ή-NMR (CDC1 3) (} 5:. 2.45 (3H, s), 2.52 (3H, s), 4.56 (2H, s), 7.02 (1H, d, J = 9 OHz), 7.18-7.33 (5H, m), 7.45-7.64 (4H, m), 8.15 (lH, dd, J = 7Hz, J = 2Hz),

8.16 (IH, dd, J = 7Hz, J = 2Hz), 8.23 (IH, d, J = 8Hz)

Example 46 (1 4)

2- (1-(3-Methyl benzo-2-yl) — 2-Methyl-5- (2-Sulfamoylphenyl) Indole-3 _ylsulfonyl) Benzoic acid (Compound 370)

Properties: colorless powder

Melting point: 2 2 0—2 2 3

_{Ή-NMR (CDC1 3) δ} : 2.41 (3Η, s), 2.45 (3Η, s), 4.82 (2Η, s), 7.14-7.34 (6Η, m), 7.50-7.81 (5Η, m), 8.16 ( IH, d, J = 8Hz), 8.23 (IH, d, J = 4Hz), 8.24 (1H, d, J = 3Hz) Example 46 (15)

2- (1— (2,3-dimethylpentyl) 1-2-methyl-5- (2-sulfamoylphenyl) Indian 1-3-ylsulfonyl] benzoic acid (Compound 37 1) Properties: colorless solid

_{Ή-NMR (CDC1 3) δ} : 2.26 (3Η, s), 2.35 (6Η, brs), 5.26 (2H, brs), 7.08 (2H, s), 7.16 (2H, q, J = 8Hz), 7.34 ( IH, d, J = 8Hz), 7.38 (IH, d, J = 7Hz), 7.52 (1H, t, J = 8Hz), 7.57-7.67 (4H, m), 8.15 (IH, d, J = 7Hz) , 8.34 (1H, dd, J = 7 Hz, J = 4 Hz), 8.39 (IH, s) Melting point: 147-1 49 ° C

Example 47 (1)-(3) The following (Compound 372) to (Compound 374) were synthesized in the same manner as in Example 33 (1).

Example 47 (1)

2- (5-bromo-2-methylindole-3-ylthio) methyl ester benzoate (Compound 372)

Properties: pale yellow powder

Melting point: 180_181

_{Ή-NMR (CDC1 3) δ} : 2.48 (3Η, s), 4.00 (3Η, s), 6.67 (IH, d, J = 8Hz),

7.09 (lH, dt, J = 8Hz, J = lHz), 7.14 (lH, dt, J = 6Hz, J = 2Hz), 7.22-7.28 (2H, m), 7.61 (IH, d, J = lHz), 8.03 (IH, dd, J = 8Hz, J = 2Hz), 8.41 (IH, brs)

Example 47 (2)

2- (5-bromo-2-methylindole-3-ylthio) benzoic acid t ert monobutyl ester (Compound 373)

Properties: yellow powder

Melting point: 79 _ 81 X:

_{Ή-NMR (CDC1 3) δ} 1.68 (9Η, s), 2.49 (3Η, s), 6.64 (lH, d, J = 8Hz),

7.04-7.13 (2H, m), 7.22-7.29 (2H, m), 7.62 (IH, s), 7.97 (IH, d, J = 7Hz),

8.33 (1H, s)

Example 47 (3)

2- (5- (2-tert-butylsulfamoylphenyl) -2-methylindole-3-ylthio) benzyl benzoate (Compound 374)

Properties: pale yellow solid

Melting point: 222 _ 223.5 ° C

_{Ή-NMR (CDC1 3) δ} : 0.84 (9Η, s), 2.51 (3H, s), 3.56 (IH, s), 5.42 (2H, s),

6.74 (IH, d, J = 8Hz), 7.05 (IH, t, J = 7Hz), 7.13 (1H, t, J = 7Hz), 7.30 (IH, d, J = 7Hz),

7.35 (IH, d, J = 7Hz), 7.37-7.43 (4H, m), 7.47-7.51 (5H, m), 8.05 (IH, d, J = 8Hz), 8.13 (1H, d, J = 8Hz), 8.67 (1H, s)

Example 48

2-(1-(3-dimethylamino-2-methylbenzoyl) _2-methyl-5_ (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzamide (compound 375)

2- (1- (3-dimethylamino-2-methylbenzoyl) -1-2-methyl-5- (2-sulfamoylphenyl) indole-3-ylsulfonyl) benzoic acid 0.08 g, WSC I 24 mg, HOB t 18 mg Then, 70 mg of ammonium chloride and 0.22 ml of triethylamine were added to 2 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 22 hours. Water was added to the reaction solution, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography (methylene chloride Z methanol = 201) to give 22 mg of the above compound.

Properties: yellow powder

Melting point: 135-137

_{'H-NMR (CDC1 3)} 6: 2.27 (3H, s), 2.42 (3H, s), 2.70 (6Η, s), 5.24 (2Η, s), 6.00 (1H, s), 6.77 (1H, s ), 7.00-7.12 (3H, m), 7.20-7.32 (2H, m), 7.48-7.55 (6H, m),

8.16 (lH, d, J = 8Hz), 8.23-8.40 (2H, m) Test example 1: Measurement of inhibitory effect on recombinant human chymase

To a 2 OmM Tris-HCl buffer (PH 8.0) containing 5 M potassium chloride and 0.01% Triton X-100, add a concentration series of test compounds and recombinant human chymase expressed in E. coli. Incubated at 37 ° C for 30 minutes. Thereafter, a synthetic substrate of succinilualanyl-aralanyl-prolyl-phenylalanine-p-nitroanilide having a final concentration of 0.5 was added, and the mixture was further incubated at 37 t: for 60 minutes. After the reaction, the amount of p-nitroaline produced by decomposition of the substrate was measured by the increase in absorbance at 405 nm. The test for each concentration series is as follows: Calculating the percent inhibition of test compounds was determined the concentration (IC _5.) Showing 50% inhibition from the concentration inhibition curves. Table 1 shows the results.

_M ^ _{(0 /} -1 _η Absorbance when test compound is added ヽ_{η Λ}

() — ( ¹ — Absorbance of test compound without added compound) ^Xl ° ° Test example 2: Measurement of inhibitory effect on α-chymotrypsin

The procedure was performed according to the method of Shujaath M et al. (Shujaath M, et al., Biochem Biophys Res Co fraction n 166 (2), 595-600, 1990). First, to a 0.1 M HE PES buffer (pH 7.5) containing 0.5 M sodium chloride, a test compound in a concentration series, and chymotrypsin were added, and the mixture was incubated at 37 ° C for 30 minutes. Thereafter, a synthetic substrate succinyl-alanyl-araniloop at an end concentration of 0.5 mM was added, and the mixture was further incubated at 37 for 60 minutes. After the reaction, the amount of p-nitroaniline produced by the decomposition of the substrate was measured by the increase in absorbance at 405 nm. Then, as in Test Example 1, IC ₅ . The value was determined. The results are shown in Table 1.

table 1

Industrial applicability

Since the compound (1) of the present invention or a salt thereof has an excellent chymase inhibitory activity, it can be used in cardiovascular diseases (such as hypertension, arteriosclerosis, congestive heart failure, myocardial infarction, cardiac and left ventricular hypertrophy, and myocardial infarction). Arterial disease, vascular hypertrophy, vascular injury accompanying angiogenesis or atheroma and restenosis after angioplasty, etc., inflammation (hepatitis, etc.), immune system disease (rheumatic, etc.), allergic disease (asthma, psoriasis, Atopy, scleroderma, etc.), eye diseases (glaucoma, cataract, etc.), diabetic complications (diabetic retinopathy, diabetic nephropathy, etc.), Prevention and treatment of collagen disease or obesity, etc., and also mucous membranes, organ protection drugs (gastrointestinal mucosa protection drugs, various tissues, organ protection drugs, etc.), cancer metastasis, prevention of invasion or improvement of survival rate after organ transplantation It is useful as a medicine. Further, the compound (2) of the present invention or a salt thereof is useful as an intermediate for synthesizing the compound (1).

Claims

The scope of the claims

1. The following general formula (1)

)Four

λ / NRI.

(1)

R '

[In the formula, R ¹ represents an amino protecting group or —COR ⁸ (where R ⁸ represents an aryl group which may have a substituent or a heteroaryl group which may have a substituent) R ² represents a hydrogen atom, an alkyl group or an aryl group which may have a substituent, R ³ is a cyano group, — COR ⁹ (where R ⁹ is a hydrogen atom, has a substituent An alkyl group, _OR ^{1 ()} (where R ^{l ()} represents a hydrogen atom, an alkyl group or an aralkyl group) or — COR ¹¹ (where R ¹¹ may have a substituent A good amino group or a cyclic amino group which may have a substituent))) or —S (〇) _n -R ¹²

(Where R ¹² represents an alkyl group, an aralkyl group, an optionally substituted aryl group or an optionally substituted heteroaryl group, and n is an integer of 0 to 2. R ⁴ , R \ R ⁶ and R ⁷ may be the same or different and may have a hydrogen atom, an alkyl group which may have a substituent, or a substituent Alkynyl group, aralkyl group, optionally substituted alkoxy group, aralkyloxy group, halogen atom, trifluoromethanesulfonyloxy group, nitro group, cyano group, hydroxy group, carboxy group, alkoxycarbonyl group Aralkyloxycarbonyl group, formyl group, alkanoyl group, benzoyl group, amino group which may have a substituent, alkyl ureido group, aryl ure which may have a substituent Group, an aryl group which may have a substituent, a heteroaryl group which may have a substituent, a cycloalkanone which may have a substituent or a cyclo which may have a substituent Indicates alkenone. ]

Or a salt thereof.

2. A medicament comprising the indole derivative according to claim 1 or a salt thereof as an active ingredient.

3. Prevention and treatment of diseases selected from cardiovascular diseases, inflammation, immune system diseases, allergic diseases, eye diseases, diabetic complications, collagen diseases and obesity, drugs for protecting mucous membranes, organs, cancer metastasis and invasion 3. The medicine according to claim 2, which is a preventive drug or a drug for improving survival rate after organ transplantation.

4. A chimaze inhibitor comprising the indole derivative according to claim 1 or a salt thereof as an active ingredient.

5. A pharmaceutical composition comprising the indole derivative according to claim 1 or a salt thereof, and a pharmaceutically acceptable carrier.

6. Prevention and treatment pharmaceutical composition for diseases selected from cardiovascular diseases, inflammation, immune system diseases, allergic diseases, eye diseases, diabetic complications, collagen diseases and obesity, and pharmaceutical compositions for protecting mucous membranes and organs The pharmaceutical composition according to claim 5, which is a pharmaceutical composition for preventing cancer metastasis and invasion or a pharmaceutical composition for improving survival rate after organ transplantation.

7. Use of the indole derivative or a salt thereof according to claim 1 as a medicament.

8. Select from cardiovascular disease, inflammation, immune system disease, allergic disease, eye disease, diabetic complication, collagen disease and obesity characterized by administering the indole derivative according to claim 1 or a salt thereof. To treat the disease.

9. The following general formula (2)

[Wherein, R ² represents a hydrogen atom, an alkyl group or an aryl group which may have a substituent, R ³ is a cyano group, — COR ⁹ (where R ⁹ is a hydrogen atom, has a substituent and which may be alkyl group, one oR ¹ "(where, R ^1" is a hydrogen atom, an alkyl group or § La alkyl group) or one COR ¹¹ (wherein, R ^{1 1} has a substituent Represents an amino group which may be substituted or a cyclic amino group which may have a substituent))) or --S (〇) _n -R ¹² (where R ¹² represents an alkyl group, an aralkyl group, a substituted or unsubstituted heteroaryl group or a substituted or unsubstituted heteroaryl group, and n is R ⁴ , R \ R ⁶ and R ⁷ may be the same or different, and have a hydrogen atom, an alkyl group which may have a substituent, or a substituent. Alkynyl group, aralkyl group, optionally substituted alkoxy group, aralkyloxy group, halogen atom, trifluoromethanesulfonyloxy group, nitro group, cyano group, hydroxy group, carboxy group, It may have an alkoxycarbonyl group, an aralkyloxycarbonyl group, a formyl group, an alkanoyl group, a benzoyl group, an amino group which may have a substituent, an alkylureido group, or a substituent. Lylureido group, aryl group optionally having substituent (s), heteroaryl group optionally having substituent (s), cycloalkanone optionally having substituent (s) or having substituent (s) And R ⁴ , R ⁵ , R ⁶ and R ⁷ are not hydrogen atoms at the same time. ]

Or a salt thereof.