JPH10158241A - Urea derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound having pharmacological activities such as a 5-HT antagonizing activity and useful for treating and preventing central nervous system diseases such as anxiety and Alzheimer's disease, etc. SOLUTION: A compound of formula I [R<1> is a lower alkyl; R<2> is a lower alkyl; R<3> is H, etc.; R<4> is phenyl, a heterocyclic group; X is methylene, iminomethylene; Y is a bond, carbonyl, etc.; (n) is 0, 1]. For example, 1-[[3-(N'- phenylamidino)phenyl]carbamoyl]-5methyl-2,3-dihydro-1H-pyrrolo [2,3-f]indole hydroiodide salt. The compound of formula I is produced by reacting a compound of formula II with a compound of the formula: R<4> -Y-(NH)n -H in the presence of an acid such as an organic acid (e.g. formic acid) or an inorganic acid (e.g. HCl) in a solvent (e.g. water, CH3 OH) usually under cooling at room temperature or under heating.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel urea derivative and a pharmaceutically acceptable salt thereof.

[0002]

BACKGROUND OF THE INVENTION It is known that several types of urea derivatives have 5- _HT2C receptor antagonism. (For example, International Publication No. WO95 / 21844, WO95 / 29177, etc.). The present invention relates to a novel urea derivative and a pharmaceutically acceptable salt thereof, and more particularly, to a novel urea derivative having pharmacological activity such as 5-hydroxytryptoamine (5-HT) antagonism and the like and a pharmaceutical thereof. A pharmaceutical composition containing the urea compound or a pharmaceutically acceptable salt thereof as an active ingredient; use of the urea compound or a pharmaceutically acceptable salt thereof as a medicament; and the urea compound. Another object of the present invention is to provide a method of using the urea compound for medical purposes, which comprises administering a pharmaceutically acceptable salt thereof to a human or animal.

[0003]

Means for Solving the Problems The urea derivative of the present invention comprises:
It can be represented by the following general formula (I). General formula: (Wherein, R ¹ represents a lower alkyl group, R ² represents a lower alkyl group and R ³ represents hydrogen, or R ² and R ³ bind to each other to form vinylene, and R ⁴ represents a substituent. X represents a methylene group or an iminomethylene group, Y represents a bond, a carbonyl group, a methylene group or an iminomethylene group, and n
Means 0 or 1)

The target compound (I) of the present invention or a salt thereof can be produced by the following reaction. Manufacturing method 1

Production method 2

Manufacturing method 3

Manufacturing method 4

Manufacturing method 5 (Wherein, R ¹ represents a lower alkyl group, R ² represents a lower alkyl group and R ³ represents hydrogen, or R ² and R ³ bind to each other to form vinylene, and R ⁴ represents a substituent. X represents a methylene group or an iminomethylene group, Y represents a bond, a carbonyl group, a methylene group or an iminomethylene group, and n
Means 0 or 1)

Further, the target compound (I) obtained by the above production methods 1 to 5 can be converted in the side chain within the scope of the compound of the present invention, as shown in the following Examples.

In addition to the above-mentioned production methods, the desired compound (I) or a salt thereof can be produced, for example, according to the methods described in the examples in the present specification, methods analogous thereto or conventional methods.

Compounds (I), (Ia), (Ib) and (I
c), (Id), (II), (III), (IV),
Suitable salts of (VI) and (IX) are the customary non-toxic pharmaceutically acceptable salts, and include salts with bases or acid addition salts, for example salts with inorganic bases, such as alkali metals Salts (eg, sodium salt, potassium salt, cesium salt, etc.), alkaline earth metal salts (eg, calcium salt, magnesium salt, etc.), ammonium salts; salts with organic salts, eg, organic amine salts (eg, triethylamine salt) , Pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt,
N, N′-dibenzylethylenediamine salt and the like); inorganic acid addition salts (eg, hydrochloride, hydrogen bromide, hydrogen iodide,
Sulfates, phosphates, etc.); organic carboxylic acid or sulfonic acid addition salts (eg, formate, acetate, trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate, p- And salts with basic or acidic amino acids (eg, arginine, aspartic acid, glutamic acid, etc.), and preferred examples thereof are acid addition salts.

In the foregoing and following description of this specification, preferred examples and explanations of various definitions included within the scope of the present invention are described in detail below.

"Lower" means 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, unless otherwise indicated.

Preferred "lower alkyl" are straight or branched chain alkyl having 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl,
Butyl, isobutyl, t-butyl, pentyl, hexyl, among which preferred are those having 1 to 4 carbon atoms, particularly preferred are methyl, ethyl, propyl or butyl .

Suitable substituents in the "phenyl group or heterocyclic group optionally having substituents" include a hydroxy group, a lower alkoxy group, a lower alkoxy lower alkoxy group, a lower alkoxy lower alkoxy lower alkoxy group, a lower alkoxy group and a lower alkoxy group. An alkyl group, an amino group, a protected amino group, a mono- or di-substituted lower alkylamino group,
Examples include a cyclic amino group, nitro, and halogen [eg, fluoro, chloro, bromo, iodo and the like].

The phenyl group or the heterocyclic group may have one or more of these substituents.

Preferred "lower alkoxy groups" include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, isopentyloxy, hexyloxy and the like.

Preferred "lower alkoxy lower alkoxy groups" include methoxymethoxy, methoxyethoxy,
Methoxypropoxy, ethoxyisopropoxy and the like can be mentioned.

Suitable "lower alkoxy lower alkoxy lower alkoxy group" include methoxymethoxyethoxy, methoxyethoxyethoxy, methoxyethoxypropoxy, ethoxymethoxyisopropoxy and the like.

Suitable mono- or di-substituted lower alkylaminos include, for example, methyl, ethyl, isopropyl,
1 by lower alkyl such as t-butyl and t-pentyl.
Or a disubstituted amino group, preferably dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, dibutylamino and the like.

Suitable "amino protecting groups" in the "protected amino group" include, for example, lower alkanoyl groups such as formyl, acetyl, propionyl, pivaloyl, hexanoyl and the like, for example, chloroacetyl, bromoacetyl, dichloroacetyl, trifluoroacetyl Mono (or di or tri) halo (lower) alkanoyl groups such as methoxycarbonyl, ethoxycarbonyl,
Propoxycarbonyl, t-butoxycarbonyl, t-
Lower alkoxycarbonyl groups such as pentyloxycarbonyl and hexyloxycarbonyl; carbamoyl groups such as benzoyl, toluoyl and naphthoyl; aroyl groups such as phenylacetyl and phenylpropionyl; and alkenyl groups such as phenylacetyl and phenylpropionyl such as phenoxycarbonyl and naphthyloxycarbonyl Aryloxycarbonyl groups such as phenoxyacetyl, phenoxypropionyl and the like; aryloxy (lower) alkanoyl groups such as phenoxyacetyl, phenoxypropionyl and the like; arylglyoxyloyl such as phenylglyoxyloyl and naphthylglyoxyloyl such as benzyloxycarbonyl and phenethyloxycarbonyl;
al (lower) alkoxycarbonyl group which may have a suitable substituent, such as p-nitrobenzyloxycarbonyl,
Acyl groups such as benzylidene, hydroxybenzylidene and the like, or unsubstituted alk (lower) alkylidene groups such as benzyl, phenethyl, benzhydryl, trityl and the like mono (or di or tri)
Al (lower) alkyl groups such as phenyl (lower) alkyl groups and the like can be mentioned.

The above-mentioned amino protecting group includes a protecting group having a function of temporarily protecting the amino group, and a protecting group often used in the field of amino acid and peptide chemistry.

The preferred “cyclic amino group” includes:
An aromatic or alicyclic group having one or more nitrogen atoms as a hetero atom, and may be a saturated or unsaturated, monocyclic or condensed polycyclic group. Further, the “cyclic amino group” may further contain one or more hetero atoms such as a nitrogen atom, an oxygen atom and a sulfur atom in the ring. Further, the cyclic amino group may be spirocyclic or bridged cyclic. The number of constituent atoms of the cyclic amino group is not particularly limited.
It is an 8- to 8-membered ring, and in the case of a bicyclic ring, it is a 7- to 11-membered ring.

Examples of such a cyclic amino group include a 1-azetidinyl group, a pyrrolidino group, a 2-pyrrolin-1-yl group, a 1-pyrrolyl group, a piperidino group, a 1,4-dihydropyridin-1-yl group, A saturated or unsaturated monocyclic group containing one nitrogen atom as a hetero atom, such as a 2,5,6-tetrahydropyridin-1-yl group or a homopiperidino group, a 1-imidazolidinyl group, a 1-imidazolyl group, Pyrazolyl group, 1-triazolyl group, 1-tetrazolyl group, 1-piperazinyl group, 1-homopiperazinyl group, 1,2-dihydropyridazin-1-yl group, 1,
2-dihydropyrimidin-1-yl group, perhydropyrimidin-1-yl group, 1,4-diazacycloheptane-
A saturated or unsaturated monocyclic group containing two or more nitrogen atoms as a hetero atom, such as a 1-yl group, an oxazolidine-3-yl group, a 2,3-dihydroisoxazole-
A saturated or unsaturated monocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 oxygen atoms as a hetero atom such as a 2-yl group or a morpholino group, a thiazolidine-3-yl group, or an isothiazolin-2-yl Or unsaturated monocyclic group containing 1 to 3 nitrogen atoms and 1 to 2 sulfur atoms as heteroatoms such as thiomorpholino group, indol-1-yl group, 1,2-dihydrobenzimidazole A condensed cyclic group such as a -1-yl group, a perhydropyrrolo [1,2-a] pyrazin-2-yl group, a spirocyclic group such as a 2-azaspiro [4,5] decane-2-yl group, And a bridged heterocyclic group such as a 7-azabicyclo [2,2,1] heptane-7-yl group.

Suitable "heterocyclic groups" are specifically defined as saturated or unsaturated, monocyclic or fused polycyclic groups having at least one heteroatom such as an oxygen, sulfur or nitrogen atom. Means a formula group.

Preferred examples of the “heterocyclic group” thus defined include a 3- to 8-membered group containing 1 to 4 nitrogen atoms,
More preferably, a 5- or 6-membered unsaturated heteromonocyclic group, for example, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridyl N-oxide, dihydropyridyl, tetrahydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl Group, triazinyl group, triazolyl group, tetrazinyl group, tetrazolyl group, etc .; nitrogen atom 1
And 5 to 5 unsaturated fused heterocyclic groups such as indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl and the like; 1 to 2 oxygen atoms and nitrogen A 3- to 8-membered unsaturated heterocyclic group containing 1 to 3 atoms, such as oxozolyl, isoxazolyl, oxadiazolyl, etc .; a 3- to 8-membered containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms Saturated heteromonocyclic group, for example, monophorino group, sydnonyl group, etc .; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, benzoxazolyl group, benzoxdiazolyl group, etc .; A 3- to 8-membered unsaturated heteromonocyclic group containing 1 to 3 nitrogen atoms and 1 to 3 nitrogen atoms, for example, thiazolyl group, isothiazolyl group Group, thiadiazolyl group; a sulfur atom 1 to 3 to 8-membered unsaturated heteromonocyclic group containing two,
For example, a thienyl group; an unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, a benzothiazolyl group and a benzothiadiazolyl group; A saturated heterocyclic monocyclic group, for example, a furyl group; an unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms, for example, a benzotiniel group; an unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms, for example, a benzofuranyl group And the like.

Preferred embodiments of R ¹ , R ² , R ³ , X, Y and R ⁴ are as follows. R ¹ is a methyl group, R ²
And R ³ combine with each other to form a vinylene group, X is an iminomethylene group, Y is a bond, R ⁴ is a phenyl group, and n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is a methylene group, R ⁴ is a phenyl group, and n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is a methylene group, R ⁴ is 3,
A 4-dimethoxyphenyl group, n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is an iminomethylene group, R ⁴ is a phenyl group, and n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is a bond, R ⁴ is 3,4-dihydroisoquinolin-1-yl, and n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
And R ² are each a methyl group, R ³ is hydrogen, X is an iminomethylene group, Y is a bond, R ⁴ is a phenyl group, and n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is an iminomethylene group, Y is a bond, R ⁴ is a morpholino group, and n is 0.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is a methylene group, R ⁴ is a 3-methoxyphenyl group, and n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is a carbonyl group, R ⁴ is 3,
A 4-dimethoxyphenyl group, n is 1.

Further, R ¹ , R ² , R ³ , X, Y and R ⁴
Preferred embodiments are as follows. R ¹
Is a methyl group, R ² and R ³ are bonded to each other to form a vinylene group, X is a methylene group, Y is a carbonyl group, R ⁴ is a pyridyl group, and n is 1.

Processes 1 to 5 for producing the desired compound (I) of the present invention
Will be described in more detail below. Production Method 1 The target compound (Ia) or a salt thereof is prepared by reacting the compound (Ia)
It can be obtained by reacting I) or a salt thereof with compound (III).

The starting material (II) or a salt thereof is a novel substance and can be obtained in the same manner as in the production examples described later.

The reaction is preferably carried out in the presence of an acid.

Suitable acids include organic acids such as formic acid,
Examples thereof include acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, and P-toluenesulfonic acid) and inorganic acids (for example, hydrochloric acid, hydrobromic acid, sulfuric acid, hydrogen chloride, and hydrogen bromide).

This hydrolysis is usually carried out with water, methanol,
The reaction is carried out in a conventional solvent or a mixture thereof which does not adversely influence the reaction of ethanol, propanol, diethyl ether, dioxane, tetrahydrofuran, N, N-dimethylformamide and the like. If the above-mentioned acids used in the reaction are liquid, they can also be used as solvents.

The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling, at room temperature or under heating.

Production Method 2 The desired compound (Ib) or a salt thereof is prepared by reacting the compound (Ib)
V) or a salt thereof can be obtained by subjecting it to an alkylation reaction.

This reaction is carried out by the binding of aldehyde (IV) and a reducing agent. In the first step, compound (IV) or a salt thereof is subjected to a condensation reaction with aldehyde (V).

In the second step, the condensation product (VI) is subjected to a reduction reaction to obtain the desired compound (Ib) or a salt thereof.

The condensation reaction is usually carried out using a conventional organic compound such as methylene chloride, acetonitrile, pyridine, tetrahydrofuran, N, N-dimethylformamide, 4-methyl-2-pentanone, benzene, toluene, xylene which does not adversely affect the reaction. It is performed in a solvent or a mixture thereof.

The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling, at room temperature or under heating.

Suitable reducing agents include metal hydrides (eg, sodium borohydride, sodium cyanoborohydride, potassium borohydride, bis-2-methoxyethoxyaluminum hydride, etc.), hydrogen, formic acid, ammonium formate , A palladium catalyst (for example, palladium-
Carbon, palladium hydroxide-carbon, palladium black, etc.).

The reduction is usually carried out with water, methanol, ethanol.
The reaction is performed in a solvent that does not adversely influence the reaction, such as toluene, propanol, N, N-dimethylformamide, or a mixture thereof.

The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling, at room temperature or under heating.

Production Method 3 The target compound (Ic) or a salt thereof is prepared by reacting the compound (Ic)
V) or a salt thereof can be obtained by reacting with compound (VII). This reaction is carried out in the same manner as in Production Method 1 described above.

Production Method 4 The target compound (Id) or a salt thereof is prepared by reacting the compound (I)
V) or a salt thereof can be obtained by reacting with compound (VIII). This reaction is carried out in the same manner as in Production Method 1 described above.

Production Method 5 The desired compound (Ie) or a salt thereof is prepared by reacting the compound (Ie)
V) or a reactive derivative thereof at an amino protecting group or a salt thereof can be obtained by reacting the compound (IX) or a reactive derivative thereof at a carboxy protecting group or a salt thereof.

As a preferred reactive derivative at the amino group of compound (IV), compound (IV) is an aldehyde,
A Schiff base imino or an enamine tautomer thereof formed by reacting with a carbonyl compound such as a ketone;
A silyl derivative formed by reacting compound (IV) with a silyl compound such as bis (trimethylsilyl) acetamide, mono (trimethylsilyl) acetamide, bis (trimethylsilyl) urea; reacting compound (IV) with phosphorus trichloride or phosgene Derivatives and the like can be mentioned.

Suitable salts of compound (IV) or a reactive derivative thereof include those exemplified for compound (I).

Suitable reactive derivatives at the carboxy group of compound (IX) include acid halides, acid anhydrides, activated amides, activated esters and the like. Preferred examples of reactive derivatives include acid chlorides; acid azides;
Substituted phosphoric acid (eg, dialkyl phosphoric acid, phenyl phosphoric acid, diphenyl phosphoric acid, dibenzyl phosphoric acid, halogenated phosphoric acid, etc.), dialkyl phosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid (eg, methanesulfonic acid, etc.), aliphatic carboxylic acid (eg, acetic acid) , Propionic acid, butyric acid, isobutyric acid, pivalic acid,
Mixed acid anhydrides with acids such as pentanoic acid, isopentanoic acid, 2-ethylbutyric acid, trichloroacetic acid, etc. or aromatic carboxylic acids (eg, benzoic acid, etc.); symmetric acid anhydrides; imidazole, 4-substituted imidazo- Dimethylpyrazole,
Activated amide with triazole or tetrazole;
Activated esters (eg, cyanomethyl ester, methoxymethyl ester, dimethyliminomethyl [(CH ₃ ) ₂
N ⁺ = CH-] ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenylthioester, p- Nitrophenyl thioester, p-cresyl thioester, carboxymethyl thioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolyl thioester, etc.); or N-hydroxy compounds (for example, N, N-dimethylhydroxylamine, 1-hydroxy- 2- (1H) -pyridone, N-
Esters with hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole, and the like. These reactive derivatives can be appropriately selected from these depending on the type of compound (IX) to be used.

Suitable salts of compound (IX) or its reactive derivative include alkali metal salts (eg, sodium salt, potassium salt, etc.), alkaline earth metal salts (eg, calcium salt, magnesium salt, etc.), ammonium salt Salt with an inorganic base such as trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt and the like; salt with compound (I) Acid addition salts as exemplified above.

The reaction is usually carried out with water, alcohol (eg, methanol, ethanol, etc.), acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N, N-dimethylformamide, The reaction is carried out in a conventional solvent such as pyridine or any other organic solvent that does not adversely influence the reaction. Among these solvents, the hydrophilic solvent can be used as a mixture with water.

In this reaction, when the compound (IX) is used in the form of a free acid or a salt thereof, the reaction is preferably carried out in the presence of a conventional condensing agent. N'-dicyclohexylcarbodiimide, N
-Cyclohexyl-N'-morpholinoethylcarbodiimide, N-cyclohexyl-N '-(4-diethylaminocyclohexyl) carbodiimide, N, N'-diethylcarbodiimide, N, N'-diisopropylcarbodiimide, N-ethyl-N'-(3 -Dimethylaminopropyl) carbodiimide, N, N'-carbonylbis-
(2-methylimidazole), pentamethyleneketene-
N-cyclohexylimine, diphenylketene-N-cyclohexylimine, ethoxyacetylene, 1-alkoxy-1-chloroethylene, trialkyl phosphite, ethyl polyphosphate, ethyl polyphosphate, phosphorus oxychloride (phosphoryl chloride), phosphorus trichloride Azide, diphenyl phosphate, thionyl chloride, oxalyl chloride, lower alkyl haloformate (eg, ethyl chloroformate, isopropyl chloroformate, etc.), triphenylphosphine, 2-ethyl-7-hydroxybenzoisoxazolium salt; 2-ethyl-5
-(M-sulfophenyl) isoxazolium hydroxide, inner salt, benzotriazol-1-yl-oxy-tris- (dimethylamino) phosphonium hexafluorophosphate, 1- (p-chlorobenzenesulfonyloxy)- 6-chloro-1H-benzotriazo-
And V, N, N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorus oxychloride, etc., so-called Vilsmeier reagents.

The reaction can also be carried out with inorganic or organic compounds such as alkali metal bicarbonate, tri (lower) alkylamine, pyridine, N- (lower) alkylmorpholine, N, N-di (lower) alkylbenzylamine and the like. It can also be performed in the presence of a base.

The reaction temperature is not particularly limited, but the reaction is usually carried out under cooling, at room temperature or under heating.

The target compound (I) of the present invention can be isolated and purified by a conventional method such as extraction, reprecipitation, fractional crystallization, recrystallization, chromatography and the like.

The desired compound (I) can therefore be converted into a salt by a conventional method.

The starting compound of this method can be produced, for example, by the method described in the following Production Examples.

Each target compound (I) may contain one or more stereoisomers such as optical isomers and geometric isomers based on asymmetric carbon atoms or double bonds. All isomers and mixtures thereof are included in the scope of the present invention.

The target compound (I) and its pharmaceutically acceptable salts include solvates (eg, clathrate compounds (eg, hydrates)).

The compound (I) of the present invention exhibits pharmacological activity such as 5-HT antagonism, especially 5HT _2c antagonism, and therefore, anxiety, depression, obsessive-compulsive disorder, migraine, anorexia Associated with central nervous system (CNS) disorders such as Alzheimer's disease, sleep disorders, bulimia, panic attacks, withdrawal symptoms due to substance abuse such as cocaine, ethanol, nicotine, and benzodiazepines, schizophrenia, or spinal cord trauma It is useful as a 5-HT antagonism for treating or preventing disorders and / or head disorders such as hydrocephalus.

In order to show the usefulness of the target compound (I),
The pharmacological activities of representative compounds of the present invention are shown below.

(1) Test method [ ³ H] -mesulazine binding The affinity of the test compound for the 5-HT _2c binding site was evaluated by evaluating the substitution of [ ³ H] -mesulazine in the rat frontal cortex. Can be determined by This method is similar to that performed by Pazos et al. In 1984.

The membrane suspension (500 μl) was mixed with [ ³ H] -mesulazine (1 nM) in Tris HC containing 4 mM CaCl ₂ and 0.1% ascorbic acid (pH 7.4).
The cells were cultured in 1 buffer at 37 ° C. for 30 minutes. Non-specific binding is measured in the presence of mianserin (1 μl). 30 nM
It used to Supiroperon of preventing the binding of 5-HT _2A sites. Test compounds (10 ⁻⁵ M) are added in 100 μl aliquots. The total volume is 1000 μl. The culture was terminated when rapid filtration occurred using a Brandel cell harvester, and the radioactivity was measured by a detector.

(2) Test compound (a) 1-[[3- (phenylamidino) phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-
Pyrrolo [2,3-f] indole hydroiodide (b) 1-[[3- (benzylaminomethyl) phenyl] carbamoyl] -5-methyl-2,3-dihydro-
1H-pyrrolo [2,3-f] indole acetate (c) 1-[[3- (3,4-dimethoxybenzylaminomethyl) phenyl] carbamoyl] -5-methyl-
2,3-dihydro-1H-pyrrolo [2,3-f] indole acetate

(3) Test Results Table 1 shows the test results.

[Table 1]

For the purpose of therapeutic or prophylactic administration, compound (I) of the present invention and pharmaceutically acceptable salts thereof may be any organic or inorganic solid suitable for oral or external intestinal or topical administration. The compound can be used in the form of a conventional pharmaceutical preparation containing the compound as an active ingredient, in admixture with a pharmaceutically acceptable carrier such as a liquid or liquid excipient. Pharmaceutical preparations include solids such as tablets, dragees, granules, capsules or liquids such as solutions, suspensions, syrups, emulsions, lemonades and the like.

If necessary, the above preparations may contain auxiliary ingredients, stabilizers, lubricants or other commonly used additives such as lactose, citric acid, tartaric acid, stearic acid, stearic acid. Magnesium, clay, sucrose,
Cornstarch, talc, gelatin, agar, pectin,
Peanut oil, olive oil, cocoa butter, ethylene glycol and the like may be contained.

The dose of Compound (I) varies depending on the age and condition of the patient, the type of disease or condition, and the type of Compound (I) applied. Generally, from about 0.01 mg to about 500 mg per day is administered to a patient. For the treatment of diseases, the compound of interest (I) of the present invention is administered at an average dose of about 0.05 mg, 0.1 mg, 0.25 m
g, 0.5 mg, 1 mg, 20 mg, 50 mg, 100
Used as mg.

Hereinafter, the present invention will be described in more detail with reference to Production Examples and Examples.

Production Example 1 3-cyanobenzoic acid (670 ml) in benzene (10 m
In 1), triethylamine (633 μl) and diphenylphosphoryl azide (973 μl) are added to the suspension and the mixture is refluxed for 2 hours. 5-methyl-2,3-dihydro-
1H-pyrrolo [2,3-f] indole (711 mg)
Is added and the mixture is refluxed for 2 hours. The reaction mixture is partitioned between benzene and 1N aqueous sodium hydroxide solution. The organic layer is separated, dried over anhydrous magnesium sulfate, filtered, and the solvent is distilled off under reduced pressure. The residue was subjected to column chromatography using silica gel and eluted with chloroform to give 1-[(3-cyanophenyl) carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f Indole (670 mg) is obtained. IR (Nujol): 2210, 1630 cm ^-1 NMR (DMSO-d ₆ , δ): 3.23-3.3.
1 (3H, m), 4.16 (2H, t, J = 8.2H
z), 6.31 (1H, d, J = 2.5 Hz), 7.1
8 (1H, d, J = 3.0 Hz), 7.26 (1H,
s), 7.41-7.54 (2H, m), 7.89 (1
H, dt, J = 2.0, 7.9 Hz), 8.04-8.
07 (2H, m), 8.75 (1H, s) Mass (m / e): 317 (M + 1)

Production Example 2 1-[(3-cyanophenyl) carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f]
Hydrogen sulfide gas is gradually passed through a solution of indole (600 mg) in pyridine (5 ml) and triethylamine (1 ml) at room temperature for 8 hours. After 36 hours, the reaction solution is diluted with water and stirred for 30 minutes. The resulting precipitate is collected by filtration, washed with water, and washed with 1-[(3-thiocarbamoylphenyl) carbamoyl] -5-methyl-2,3-dihydro-1H-.
Pyrrolo [2,3-f] indole (641 mg) is obtained. IR (Nujol): 1640 cm ^-1 NMR (DMSO-d ₆ , δ): 3.26 (2H,
t), 4.17 (2H, t), 6.29 (1H, d, J
= 2.6 Hz), 7.17 (1H, d, J = 3.0H)
z), 7.26-7.43 (3H, m), 7.72-
7.76 (1H, m), 8.04 (1H, s), 8.1
1 (1H, s), 8.60 (1H, s), 9.43 (1
H, s), 9.81 (1H, s) Mass (m / e): 351 (M + 1)

Production Example 3 N-N-dimethyl of 1-[(3-thiocarbamoylphenyl) carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] indole (600 mg) To a solution of formamide (10 ml) is added methyl iodide (3 ml). After 24 hours, the reaction solution is diluted with water and extracted twice with ethyl acetate. The extracts are combined, dried over anhydrous magnesium sulfate, filtered, and the solvent is distilled off under reduced pressure. The residue was subjected to column chromatography on silica gel, eluting with 10% methanol in chloroform, to give 1-[[3-[(methylthio) (imino) methyl] phenyl] carbamoyl] -5-methyl-2,3. −
Dihydro-1H-pyrrolo [2,3-f] indole; hydroiodide. The compound is provided without purification.

Production Example 4 To a solution of 3-cyanoaniline (1.3 g) in tetrahydrofuran (15 ml) was added 1,1'-carbonyldiimidazole (1.78 g). The mixture is stirred at room temperature for 5 hours. To this solution is added 5-dimethylaminoindoline (2.02 g) and the mixture is stirred overnight at room temperature.
The solvent of the resulting mixture is evaporated and partitioned between chloroform and water. The organic layer is separated, dried over magnesium sulfate, filtered, evaporated and subjected to column chromatography using silica gel, eluting with chloroform. The obtained substance was recrystallized from chloroform to give 1-
[(3-Cyanophenyl) carbamoyl] -5- (dimethylamino) indoline (801 mg) is obtained. IR (Nujol): 1650 cm ^-1 NMR (DMSO-d ₆ , δ): 2.83 (6H,
s), 3.09-3.18 (2H, m), 4.04-
4.14 (2H, m), 6.53 (1H, dd, J =
2.6, 8.8 Hz), 6.67 (1H, s), 7.4
0-7.53 (2H, m), 7.70 (1H, d, J =
8.8 Hz), 7.86 (1H, dt, J = 1.9,
3.8 Hz), 8.05 (1H, s), 8.69 (1
H, s) Mass (m / e): 307 (M + 1)

Production Example 5 The following compound is obtained in the same manner as in Production Example 2. 1-[(3
-Thiocarbamoylphenyl) carbamoyl] -5-
(Dimethylamino) indoline. IR (Nujol): 1705, 1640, 161
0.1570 cm ^-1 NMR (DMSO-d ₆ , δ): 2.82 (6H,
s), 3.08-3.17 (2H, m), 3.98-
4.13 (2H, m), 6.53 (1H, dd, J =
2.5, 8.8 Hz), 6.67 (1H, s), 7.2
5-7.41 (2H, m), 7.65 (2H, d, J =
8.8 Hz), 8.32 (1 H, s), 8.55 (1
H, s), 9.45 (1H, s), 9.84 (1H,
s) Mass (m / e): 341 (M + 1)

Production Example 6 The following compound is obtained in the same manner as in Production Example 3. 1-[[3
-[(Methylthio) (imino) methyl] phenyl] carbamoyl] -5- (dimethylamino) indoline hydroiodide IR (nujol): 1680, 1630 cm ^-1 NMR (DMSO-d ₆ , δ): 2 .86 (3H,
s), 3.30 (2H, t, J = 8.8 Hz), 3.5
9 (6H, s), 4.26 (2H, t, J = 8.5H)
z), 7.49-7.98 (6H, m), 8.24 (1
H, s), 9.08 (1H, s) Mass (m / e): 307 (M-SMe) Mass (m / e): 355 (M + 1)

Production Example 7 1-[(3-cyanophenyl) carbamoyl] -5-
Methyl-2,3-dihydro-1H-pyrrolo [2,3-
f] Rhodium (alumina support) (600 mg) is added to a solution of indole (930 mg) in tetrahydrofuran (25 ml) and a 10N ammonia solution in methanol. The mixture is hydrogenated at 3 atmospheres at room temperature for 5 hours. The reaction mixture is filtered and the solvent is distilled off under reduced pressure. The residue was subjected to column chromatography on silica gel, eluting with a mixture of methanol and chloroform (1: 4 v / v) to give 1-[[3- (aminomethyl) phenyl] carbamoyl] -5-methyl-2. , 3-Dihydro-1H-
Pyrrolo [2,3-f] indole (930 mg) is obtained. IR (Nujol): 1650 cm ^-1 NMR (DMSO-d ₆ , δ): 3.25 (2H,
t, J = 8.1 Hz), 3.73 (3H, s), 4.1
5 (1H, t, J = 8.2 Hz), 6.29 (1H,
d, J = 2.8 Hz), 6.98 (1H, d, J = 7.
5Hz), 7.16-7.25 (3H, m), 7.43
(1H, d, J = 7.9 Hz), 7.55 (1H,
s), 8.03 (1H, s), 8.38 (1H, s) Mass (m / e): 321 (M + 1)

Example 1 1-[[3-[(Methylthio) (imino) methyl] phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] indole iodide A mixture of the hydrochloride (120 mg), aniline (68 mg) and acetic acid (42 μl) in methanol (5 ml) was heated to 80 ° C.
And heat for 3 hours. After evaporation of the solvent, the residue was subjected to column chromatography using silica gel, eluting with 10% methanol in 10% chloroform and 1-[[3
-(N'-phenylamidino) phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] indole hydroiodide (45 m
g). mp: 158-165 ° C IR (Nujol): 1540 cm ^-1 NMR (DMSO-d ₆ , δ): 3.31 (2H,
t, J = 8.0 Hz), 3.73 (3H, s), 4.1
8 (2H, t, J = 8.3 Hz), 6.30 (1H,
d, J = 2.8 Hz), 6.98-7.49 (1H,
m), 7.80 (2H, d, J = 7.6 Hz), 8.0
5 (1H, s), 8.18 (1H, s), 8.64 (1
H, s) Mass (m / e): 410 (M + 1)

Example 2 The following compounds were obtained in the same manner as in Example 1. 1-[[3-
(N′-phenylamidino) phenyl] carbamoyl] -5- (dimethylamino) indoline hydroiodide mp: 171-191 ° C. IR (nujol): 1640,1580 cm ⁻¹ NMR (DMSO-d ₆ , δ) ): 3.70 (6H,
s), 4.28 (2H, t, J = 8.6 Hz), 7.4
8-7.99 (11H, m), 8.23 (1H, s),
9.05-9.10 (2H, m), 9.85 (1H,
s) Mass (m / e): 400 (M + 1)

Example 3 The following compounds were obtained in the same manner as in Example 1. 1-[(3
-Amidinophenyl) carbamoyl] -5- (dimethylamino) indoline hydroiodide mp: 164-171 ° C IR (nujol): 1670, 1540 cm ^-1 NMR (DMSO-d ₆ , δ): 3.29 (2H,
t, J = 8.1 Hz), 3.57 (6H, s), 4.2
5 (2H, t, J = 8.5 Hz), 7.39-7.55
(2H, m), 7.71-8.05 (4H, m) Mass (m / e): 324 (M + 1)

Example 4 1-[[3- (Aminomethyl) phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo
[2,3-f] To a solution of indole (80 mg) in toluene (15 ml) is added benzaldehyde (29 mg) and the mixture is refluxed for 3 hours. After evaporation of the solvent, the residue is suspended in methanol (5 ml) and sodium borohydride (28 mg) is added. The mixture is stirred at 70 ° C. for 30 minutes and the solvent is distilled off under reduced pressure. The residue is partitioned between water and chloroform. The organic layer is separated, dried over anhydrous sodium sulfate, subjected to column chromatography using silica gel and eluted with chloroform. The oil obtained is dissolved in methanol and acetic acid (29 mg) is added. After evaporating the solvent, the obtained substance was triturated with diethyl ether to give 1-[[3- (benzylaminomethyl)
[Phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] indole acetate (94 mg) is obtained. mp: 44-48 ° C IR (Nujol): 1640 cm ^-1 NMR (DMSO-d ₆ , δ): 1.91 (4H,
s), 3.25 (2H, t, J = 8.1 Hz), 3.6
7 (2H, s), 3.73 (2H, s), 4.15 (2
H, t, J = 8.1 Hz), 6.29 (1H, d, J =
2.8 Hz), 6.98 (1H, d, J = 7.7H)
z), 6.96-7.56 (11H, m), 8.03.
(1H, s), 8.38 (1H, s) Mass (m / e): 411 (M + 1)

Example 5 The following compounds were obtained in the same manner as in Example 4. 1-[[3-
(3,4-dimethoxybenzylaminomethyl) phenyl] carbamoyl] -5-methyl-2,3-dihydro-
1H-pyrrolo [2,3-f] indole acetate salt mp: 155-158 ° C IR (nujol): 1670, 1610 cm ^-1 NMR (DMSO-d ₆ , δ): 1.90 (3H,
s), 3.2-3.3 (2H, m), 3.64-3.6.
6 (4H, m), 3.73 (6H, s), 3.75 (3
H, s), 4.1-4.3 (2H, m), 6.30 (1
H, s), 6.80-7.10 (4H, m), 7.15.
−7.30 (4H, m), 7.40-7.50 (1H,
m), 7.59 (1H, s), 8.03 (1H, s),
8.38 (1H, s) Mass (m / e): 471 (M + 1)

Example 6 1-[[3- (Aminomethyl) phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] -indole (250 mg) in methanol (10 ml) (Methylthio) iminomethylbenzene hydroiodide (240 μl)
mg). The mixture is heated at 75 ° C. for 5 hours and the solvent is distilled off under reduced pressure. The residue was subjected to column chromatography on silica gel, eluting with 5% methanol in chloroform, to give 1-[[3-[[(imino) (phenyl) methyl] aminomethyl] phenyl] carbamoyl] -5-methyl -2,3-dihydro-1H-pyrrolo [2,3-f] indole hydroiodide (172
mg). mp: 154-170 ° C IR (Nujol): 1650, 1610 cm ^-1 NMR (DMSO-d ₆ , δ): 3.26 (2H,
t, J = 8.3 Hz), 3.73 (3H, s), 4.1
6 (2H, t, J = 8.2 Hz), 4.68 (2H,
s), 6.30 (1H, d, J = 2.9 Hz), 7.0
5 (1H, d, J = 7.3 Hz), 7.18 (1H,
d, J = 2.9 Hz), 7.26 (1H, s), 7.3
4 (1H, t, J = 7.7 Hz), 7.49 (1H,
d, J = 8.0 Hz), 7.61-7.84 (6H,
m), 8.04 (1H, s), 8.32 (1H, s),
8.52 (1H, s), 9.64 (2H, s) Mass (m / e): 424 (M + 1)

Example 7 The following compounds were obtained in the same manner as in Example 6. 1-[[3-
[(3,4-dihydroisoquinolin-1-yl) aminomethyl] phenyl] carbamoyl] -5-methyl-2,
3-dihydro-1H-pyrrolo [2,3-f] indole hydroiodide mp: 195-198 ° C IR (Nujol): 1640 cm ^-1 NMR (DMSO-d ₆ , δ): 3.05 ( 2H,
t), 3.25 (2H, t), 3.56 (2H, t),
3.73 (3H, s), 4.14 (2H, t, J = 8.
3 Hz), 4.68 (2H, s), 6.29 (1H,
d), 7.03 (1H, d, J = 7.8 Hz), 7.1
8 (1H, d, J = 2.7 Hz), 7.2-7.4 (2
H, m), 7.4-7.6 (3H, m), 7.6-7.
8 (2H, m), 8.00 (1H, s), 8.08 (1
H, d, J = 7.8 Hz), 8.49 (1H, s),
9.8-10.2 (2H, m) Mass (m / e): 450 (M + 1)

Example 8 The following compounds were obtained in the same manner as in Example 1. 1-[[3-
(Morpholinoiminomethyl) phenyl] carbamoyl]
-5-methyl-2,3-dihydro-1H-pyrrolo [2,
3-f] Indole hydroiodide m. p. : 185-187 ° C IR (Nujol): 1650 cm ^-1 NMR (DMSO-d6 _, δ): 3.07 (4H,
m), 3.28 (2H, t, J = 8 Hz), 3.7
4 (3H, s), 3.77 (4H, m), 4.17
(2H, t, J = 8 Hz), 6.32 (1H, d, J
= 3 Hz), 7.20 (1H, d, J = 3 Hz),
7.24 (1H, s), 7.28 (1H, s),
7.54 (1H, t, J = 8 Hz), 7.78 (1
H, br. d, J = 8 Hz), 7.95 (1H,
m), 8.03 (1H, br.d) Mass: 404 (M + 1 ⁺ )

Example 9 The following compounds were obtained in the same manner as in Example 4. 1-[[3-
(3-methoxybenzylaminomethyl) phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] indole fumarate m. p. : 128-130 ° C IR (Nujol): 1640 cm ^-1 NMR (DMSO-d _6, δ): 3.25 (2H,
t, J = 8 Hz), 3.73 (3H, s), 3.7
6 (3H, s), 3.89 (2H, br.s),
3.90 (2H, br.s), 4.15 (2H, t,
J = 8 Hz), 6.30 (1H, d, J = 3 Hz),
6.57 (2H, s), 6.85 (1H, d, J =
3 Hz), 6.97 (3H, m), 7.23 (5
H, m), 7.53 (1H, t, J = 8 Hz),
7.65 (1H, br.s), 8.03 (1H, b.
r. s), 8.45 (1H, br.s) Mass: 441 (M + 1 ⁺ )

Example 10 1- [3- (aminomethyl) phenylcarbamoyl]-
5-methyl-2,3-dihydro-1H-pyrrolo [2,3
-F] indole (0.1 g) in chloroform (10
ml) Triethylamine (0.131ml)
And 3,4-dimethoxybenzoyl chloride (0.09
4 g) is added. The solution was stirred at room temperature for 1 hour, washed successively with water and an aqueous solution of sodium hydrogen carbonate, dried over magnesium sulfate, subjected to chromatography using silica gel, and mixed with chloroform and methanol (chloroform: methanol = 10: 1). And eluted with 1-[[3
-(3,4-Dimethoxybenzoylaminomethyl) phenyl] carbamoyl] -5-methyl-2,3-dihydro-1H-pyrrolo [2,3-f] indole (124 m
g). m. p. : 152-154 ° C IR (Nujol): 1640, 1620 c
m ^-1 NMR (DMSO-d _6, δ): 3.24 (2H,
t, J = 8 Hz), 3.72 (3H, s), 3.8
1 (6H, m), 4.13 (2H, t, J = 8H
z), 4.46 (2H, d, J = 6 Hz), 6.2
9 (1H, d, J = 3 Hz), 7.00 (2H,
m), 7.17 (1H, d, J = 3 Hz), 7.24
(1H, s), 7.49 (1H, s), 8.01
(1H, br.s), 8.43 (1H, br.s),
8.91 (1H, br.s) Mass: 485 (M + 1 ⁺ )

Example 11 The following compounds were obtained in the same manner as in Example 10. 1-[[3
-(Nicotinoylaminomethyl) phenyl] carbamoyl] -5-methyl-1,2,3,5-tetrahydropyrrolo [2,3-f] indole m. p. : 218-219 ° C IR (Nujol): 1670, 1640 cm
^-1 NMR (DMSO-d6 _{, [} delta]): 3.24 (2H,
t, J = 8 Hz), 3.73 (3H, s), 4.1
4 (2H, t, J = 8 Hz), 4.50 (2H, d,
J = 6 Hz), 6.30 (1H, br.s), 6.
97 (1H, d, J = 7 Hz), 7.21 (3H,
m), 7.55 (3H, m), 8.01 (1H,
s), 8.26 (1H, d, J = 7 Hz), 8.4
4 (1H, s), 8.71 (1H, br.s),
9.08 (1H, s), 9.26 (1H, br.s) Mass: 426 (M + 1 ⁺ )

Example 12 3-[(isoquinolin-1-yl) aminomethyl] aniline (124 mg) in dimethylformamide (1 ml)
4-nitrophenyl chloroformate (101 mg) is added at 5 ° C. to a solution of and pyridine (40 μl). The mixture is stirred at 5 ° C. for 30 minutes and at room temperature for 30 minutes.
To the mixture is added 5-methyl-1,2,3,5-tetrahydropyrrolo [2,3-f] indole (86 mg) and triethylamine (0.14 ml). Stir at room temperature for 24 hours and pour into ice water (20 ml). After 30 minutes, the product is filtered, washed with water, dissolved in chloroform, washed with brine, dried over magnesium sulfate and filtered.
The solvent was distilled off and the residue was subjected to column chromatography using silica gel to give 1-[[3-[(isoquinoline-1).
-Yl) aminomethyl] phenyl] carbamoyl] -5
-Methyl-1,2,3,5-tetrahydropyrrolo [2,
This gives 3-f "indole (117 mg). m. p. 212-214 ° C IR (Nujol) 3450, 1670 cm ^-1 NMR (dmso, δ): 3.22 (2H, t, J =
8.2), 3.72 (3H, s), 4.11 (2
H, t, J = 8.2), 4.74 (2H, d, J =
5.8), 6.29 (1H, d, J = 2.9),
6.89 (1H, d, J = 5.7), 7.00 (1
H, d, J = 7.6), 7.15-7.23 (5H,
m), 7.42-7.73 (5H, m), 7.83
(1H, d, J = 5.8), 7.96-8.05 (2
H, m), 8.33 (1H, d, J = 8.4),
8.38 (1H, s) ms: 448 (m + 1)

Example 13 The following compounds were obtained in the same manner as in Example 12. 1-[[3
-[(Quinolin-2-yl) aminomethyl] phenyl]
Carbamoyl] -5-methyl-1,2,3,5-tetrahydropyrrolo [2,3-f] indole m. p. 92-102 ° C IR (KBr) 1658 cm ^-1 ms: 448 (m + 1) NMR (dmso-d ₆ , δ): 3.23 (2H,
t, J = 8.3) 3.72 (3H, s), 4.13
(2H, t, J = 8.3), 4.63 (2H, d, J
= 5.7), 6.29 (1H, dJ = 2.9),
6.85 (1H, d, J = 8.9), 7.00-7.
29 (5H, m), 7.39-7.52 (4H,
m), 7.55-7.65 (2H, m), 7.86
(1H, d, J = 8.9), 8.01 (1H, s),
8.41 (1H, s)

Example 14 The following compounds were obtained in the same manner as in Example 12. 1-[[3
-[(Quinazolin-4-yl) aminomethyl] phenyl] carbamoyl] -5-methyl-1,2,3,5-tetrahydropyrrolo [2,3-f] indole m. p. 142-145 ° C IR (KBr) 1656 cm ^-1 ms: 449 (m + 1) NMR (dmso-d ₆ , δ): 3.22 (2H,
t, J = 8.2) 3.72 (3H, s), 4.11
(2H, t, J = 8.2), 4.79 (2H, d, J
= 5.8), 6.29 (1H, dJ = 2.6),
6.9-7.05 (1H, m), 7.17 (1H,
d, J = 2.6), 7.20-7.27 (2H,
m), 7.46-7.54 (3H, m), 7.67
−7.78 (2H, m), 8.00 (1H, s),
8.33 (1H, d, J = 2.9), 8.40 (1
H, s), 8.46 (1H, s), 8.86 (1
H, t, J = 5.6).

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Yuka Noda 5-8-D73-203, Tsuundai, Suita-shi, Osaka (72) Inventor Masayuki Kato 6-16-12, Goryo Oedayamacho, Nishikyo-ku, Kyoto, Kyoto

Claims (1)

[Claims] 1. The general formula: (Wherein, R ¹ represents a lower alkyl group, R ² represents a lower alkyl group and R ³ represents hydrogen, or R ² and R ³ bind to each other to form vinylene, and R ⁴ represents a substituent. X represents a methylene group or an iminomethylene group, Y represents a bond, a carbonyl group, a methylene group or an iminomethylene group, and n
Means 0 or 1. ) Or a salt thereof.