JP2969207B2 - Oxytocin antagonist - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to oxytocin antagonists.

[0002]

2. Description of the Related Art The benzoheterocyclic compound which is an active ingredient of the oxytocin antagonist of the present invention is a known compound and is known to have a vasopressin action (European Patent No. 45,097). Book). The present inventors have further studied such a benzoheterocyclic compound, and as a result, have found that the compound is effective as an oxytocin antagonist. The present invention has been completed based on such findings.

[0003]

According to the present invention, the general formula (1)

[0004]

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[Wherein R ¹ represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group or a lower alkoxy group which may have a lower alkyl group as a substituent. R ² has a hydrogen atom, a halogen atom, a lower alkoxy group, a phenyl lower alkoxy group, a hydroxyl group, a lower alkyl group, an amino group which may have a lower alkyl group, a carbamoyl-substituted lower alkoxy group, and a lower alkyl group as a substituent Represents a certain amino-substituted lower alkoxy group or a benzoyloxy group which may have a halogen atom as a substituent on a phenyl ring. R ³ represents a group —NR ⁴ R ⁵ or a group —CONR ¹¹ R ¹² . R ⁴ represents a hydrogen atom, a benzoyl group or a lower alkyl group which may have a halogen atom as a substituent on the phenyl ring. R ⁵ is a group

[0006]

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[R ¹⁶ is a halogen atom, a lower alkyl group, a hydroxyl group, a lower alkoxy group, a lower alkanoyloxy group, a lower alkylthio group, a lower alkanoyl group, a carboxy group, a lower alkoxy group which may have a halogen atom or a hydroxyl group as a substituent. Amino group, phenyl group, cycloalkyl group, lower alkanoyloxy-substituted lower alkoxy group, carboxy-substituted lower alkoxy group, carboxy-substituted lower alkoxy group, which may have carbonyl group, cyano group, nitro group, lower alkyl group or lower alkanoyl group A carbamoyl-substituted lower alkoxy group, a hydroxyl-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a phthalimide-substituted lower alkoxy group, an aminocarbonyl lower alkoxy group having a lower alkyl group as a substituent or Group ^{-O-A-NR 6 R 7} (A
Represents a lower alkylene group, R ⁶ and R ⁷ are the same or different and represent a hydrogen atom, a lower alkyl group which may have a hydroxyl group as a substituent, a lower alkanoyl group or a benzoyl group. R ⁶ and R ⁷ may form a 5- or 6-membered saturated heterocycle with or without a nitrogen atom to be bonded via a nitrogen atom or an oxygen atom. The heterocyclic ring may be substituted with a group selected from the group consisting of a piperidinyl group and a lower alkyl group). m represents an integer of 0 to 3], a phenyl lower alkoxycarbonyl group,
Lower alkanoyl group, phenyl lower alkanoyl group, cycloalkyl lower alkanoyl group, cycloalkylcarbonyl group, tricyclo [3.3.1.1] decanylcarbonyl group, naphthylcarbonyl group, pyridylcarbonyl group, furoyl group, tenoyl group, A phenoxy lower alkanoyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group as a substituent, a lower alkoxy group and an amino group which may have a lower alkanoyl group as a substituent on a phenyl ring, phthalimide Substituted lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, carboxy lower alkanoyl group, naphthyloxy lower alkanoyl group, halogen-substituted lower alkanoyl group,
Base

[0008]

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(R ⁸ represents a hydrogen atom, a lower alkyl group, a phenyl lower alkoxycarbonyl group, a carbamoyl lower alkyl group, an amino lower alkanoyl group or a lower alkanoyl group which may have a lower alkyl group as a substituent), a phenyl ring Anilino carbonyl group, phenoxycarbonyl group which may have a lower alkyl group as a substituent on the above, phenylsulfonyl group which may have a group selected from the group consisting of a halogen atom and a lower alkyl group as a substituent on a phenyl ring , quinolyl sulfonyl group or a group ^{-COB- (CO) n -NR 9 R} 10 (B is a lower alkylene group, n represents an integer of 0 or 1 .R ⁹ and R ¹⁰
Are the same or different hydrogen atom, a lower alkyl group which may have a hydroxyl group as a substituent, a cycloalkyl group, a phenyl lower alkyl group, a lower alkanoyl group, a lower alkenyl group, a phenoxy lower alkyl group, a substituent on the phenyl ring Amino lower alkyl group which may have a lower alkanoyl group, lower alkyl group, phenyl group which may have 1 to 3 groups selected from the group consisting of lower alkoxy and halogen atom, phthalimide-substituted lower alkyl group, as a substituent It represents an amino lower alkyl group which may have a lower alkanoyl group, a lower alkynyl group or an amino lower alkyl group which may have a lower alkyl group as a substituent. Further, R ⁹ and R ¹⁰ may form a 5- to 6-membered saturated heterocyclic ring together with or without a nitrogen atom to be bonded via a nitrogen atom or an oxygen atom. The heterocyclic ring may be substituted with a group selected from the group consisting of a lower alkyl group, a lower alkoxycarbonyl group and a piperidinyl group). R ¹¹ represents a hydrogen atom or a lower alkyl group. R ¹² represents a cycloalkyl group or a phenyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group, a lower alkyl group and a halogen atom on a phenyl ring. W is a group-(CH ₂ ) _p- (p
3-5 integer) or a group _{-CH = CH- (CH 2) q} -
(Q is an integer of 1 to 3). Base - (CH _{2) p} - and group _{-CH = CH- (CH 2) q} - carbon atoms is an oxygen atoms in sulfur atom, a sulfinyl group, a sulfonyl group or a group -NR ¹³ - (R ¹³ is a hydrogen atom , A cycloalkyl group or a lower alkyl group.). The group — (CH ₂ ) _p — or the group —CH ＝ CH— (CH ₂ ) _q —
In some lower alkyl groups that may have a hydroxyl group as a substituent, lower alkoxycarbonyl group, carboxy group,
A hydroxyl group, an oxo group, a lower alkanoyloxy group which may have a halogen atom as a substituent, an amino lower alkyl group which may have a group selected from a lower alkyl group and a lower alkanoyl group as a substituent, a lower alkanoyloxy Substituted lower alkyl group, lower alkylsulfonyloxy lower alkyl group, azide lower alkyl group, group -OCH _2- , aminocarbonyloxy group which may have a lower alkyl group as a substituent, lower alkoxy group, lower alkoxycarbonyl-substituted lower alkoxy group Group, a carboxy-substituted lower alkoxy group, an aminocarbonyl lower alkoxy group which may have a lower alkyl group as a substituent, an amino lower alkoxy group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent Group, phthalimide-substituted lower alkoxy group, hydroxyimino group, a lower alkanoyloxy imino group, a lower alkylidene group, a halogen atom, azido group, sulfo oximino group, group

[0010]

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(R ¹⁷ represents a hydrogen atom or a lower alkyl group), a hydrazino group, a pyrrolyl group, an amino-lower alkanoyloxy group which may have a lower alkyl group as a substituent, a group -OA-CONR ¹⁸ R ¹⁹ (a is the same .R ¹⁸ and R ¹⁹ are the same or different, a hydrogen atom, a lower alkyl group, a carbamoyl-substituted lower alkyl group, a hydroxyl-substituted lower alkyl group or a pyridyl-lower alkyl group. Further, and this R ¹⁸ R ¹⁹ may form a 5- or 6-membered saturated heterocyclic ring with or without a nitrogen atom, an oxygen atom or a sulfur atom together with the nitrogen atom to which they are bonded. A lower alkyl group, a lower alkanoyl group or a carbamoyl group may be substituted) and a group — (CO) _n NR ¹⁴ R ¹⁵ (n is the same as above. R ¹⁴ and R ¹⁵ are Same or different hydrogen atom, lower alkyl group, lower alkenyl group, lower alkanoyl group, cycloalkyl group, oxiranyl-substituted lower alkyl group, lower alkoxy group as a substituent, hydroxyl group and amino having a lower alkyl group as a substituent A lower alkyl group having 1 to 2 groups selected from the group consisting of a lower group, a phenyl lower alkyl group, a pyridyl lower alkyl group, a lower alkylsulfonyl group, a benzoyl group, a lower alkoxycarbonyl group, an anilinocarbonyl group, and a lower substituent. Aminocarbonyl group which may have an alkyl group, cyano-substituted lower alkyl group, lower alkoxycarbonyl-substituted lower alkyl group, carbamoyl-substituted lower alkyl group, carboxy-substituted lower alkyl group, tetrahydropyranyloxy-substituted lower alkyl group, lower alkano Luoxy-substituted lower alkyl group, piperidinyl group which may have a phenyl lower alkyl group as a substituent on the piperidine ring, halogen-substituted lower alkanoyl group, imidazolyl-substituted lower alkanoyl group, lower alkyl group and lower alkoxycarbonyl group as substituents An amino lower alkanoyl group which may have a selected group, an aminocarbonyl lower alkyl group or a phenyl lower alkoxycarbonyl group which may have a lower alkyl group as a substituent, and R ¹⁴ and R ¹⁵ represent a nitrogen atom to be bonded. 5-6 with or without a nitrogen or oxygen atom with the atom
It may form a membered saturated heterocyclic ring. The heterocyclic ring may be substituted with 1 to 3 groups selected from the group consisting of a lower alkyl group, a phenyl lower alkyl group and a lower alkanoyl group. An oxytocin antagonist comprising at least one selected from the group consisting of a benzoheterocyclic compound represented by the formula (I) and a salt thereof as an active ingredient is provided.

The benzoheterocyclic compound of the general formula (1) and salts thereof all have excellent oxytocin antagonist activity.

The oxytocin antagonist of the present invention has, for example, an inhibitory action on uterine smooth muscle, an inhibitory action on milk release, an inhibitory action on prostaglandin synthesis and release, and a vasodilatory action. It is effective for prevention of childbirth and prevention or treatment of dysmenorrhea.

Each of the groups represented by the general formula (1) is more specifically as follows. Examples of the lower alkoxy group include linear or branched C1-C6 alkoxy groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy groups.

As the lower alkyl group, for example, methyl,
Examples thereof include linear or branched alkyl groups having 1 to 6 carbon atoms, such as ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, and hexyl groups.

As the halogen atom, for example, a fluorine atom,
Examples include a chlorine atom, a bromine atom and an iodine atom.

Examples of the amino group which may have a lower alkyl group include amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, Dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-
N-propylamino, N-methyl-N-butylamino,
Examples of a substituent such as an N-methyl-N-hexylamino group include an amino group having 1 or 2 straight or branched alkyl groups having 1 to 6 carbon atoms.

Examples of the lower alkenyl group include linear or branched alkenyl having 2 to 6 carbon atoms such as vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl and 2-hexenyl. Groups.

Examples of the lower alkyl group which may have a halogen atom or a hydroxyl group as a substituent include hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3 -Dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,
5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoro Methyl, dibromomethyl, 2-chloroethyl, 2,2
2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl,
4,4,4-trichlorobutyl, 4-fluorobutyl,
1 to 6 carbon atoms which may have 1 to 3 halogen atoms or hydroxyl groups as substituents such as 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl and 5,6-dichlorohexyl groups. A linear or branched alkyl group can be exemplified.

The lower alkylene group includes, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene C1 of group etc.
To 6 linear or branched alkylene groups.

Examples of the lower alkanoyloxy group include straight-chain alkanoyloxy groups such as formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy and hexanoyloxy groups. A chain or branched alkanoyloxy group may be mentioned.

Examples of the lower alkylthio group include straight-chain or branched-chain alkylthio groups having 1 to 6 carbon atoms such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio and hexylthio.

Examples of the lower alkanoyl group include linear or branched alkanoyl groups having 1 to 6 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl groups.

Examples of the lower alkoxycarbonyl group include linear groups having 1 to 6 carbon atoms such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl. Alternatively, a branched alkoxycarbonyl group can be exemplified.

The amino group which may have a lower alkyl group or a lower alkanoyl group includes, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethyl Amino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N- Hexylamino, N-methyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino,
As a substituent such as N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, a group having 1 to 6 carbon atoms And a linear or branched alkyl group having 1 to 6 carbon atoms and an amino group which may have 1 to 2 groups selected from a linear or branched alkanoyl group having 1 to 6 carbon atoms.

Examples of the cycloalkyl group include those having 3 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
To 8 cycloalkyl groups.

The lower alkanoyloxy group-substituted lower alkoxy group includes, for example, acetyloxymethoxy,
Propionyloxyethoxy, 1-butyryloxyethoxy, 3-acetyloxypropoxy, 4-acetyloxybutoxy, 4-isobutyryloxybutoxy, 5-
Carbon number of pentanoyloxypentyloxy, 6-acetyloxyhexyloxy, 6-tert-butylcarbonyloxyhexyloxy, 1,1-dimethyl-2-hexanoyloxyethoxy, 2-methyl-3-acetyloxypropoxy group, etc. A straight-chain or branched-chain alkanoyloxy group having 2 to 6 carbon atoms may be a straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms.

Examples of the carbamoyl group-substituted lower alkoxy group include carbamoylmethoxy, 2-carbamoylethoxy, 1-carbamoylethoxy, 3-carbamoylpropoxy, 4-carbamoylbutoxy, 5-carbamoylpentyloxy, 6-carbamoylhexyloxy, 1-dimethyl-2-carbamoylethoxy, 2
And a carbamoylalkoxy group in which the alkoxy moiety such as -methyl-3-carbamoylpropoxy group is a linear or branched alkoxy group having 1 to 6 carbon atoms.

Examples of the hydroxy-substituted lower alkoxy group include hydroxymethoxy, 2-hydroxyethoxy,
-Hydroxyethoxy, 3-hydroxypropoxy,
2,3-dihydroxypropoxy, 4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl-2-hydroxyethoxy, 5-hydroxypentyloxy, 6-hydroxyhexyloxy, 2-methyl-
1 to 6 carbon atoms having 1 to 3 hydroxyl groups such as 3-hydroxypropoxy and 2,3,4-trihydroxybutoxy groups
And a straight-chain or branched-chain alkoxy group.

Examples of lower alkoxycarbonyl-substituted lower alkoxy groups include methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3-ethoxycarbonylpropoxy,
4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonyl A straight-chain or branched-chain alkoxycarbonyl group having 1 to 6 carbon atoms in which an alkoxycarbonyl moiety such as an ethoxy or hexyloxycarbonylmethoxy group is a straight-chain or branched-chain alkoxycarbonyl group having 1 to 6 carbon atoms. be able to.

Examples of the carboxy-substituted lower alkoxy group include carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, The carbon number of the alkoxy moiety such as 1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy group is 1 to 1
And a carboxyalkoxy group which is a straight-chain or branched alkoxy group of No. 6.

Examples of the phthalimido-substituted lower alkoxy group include phthalimidomethoxy, 2-phthalimidoethoxy, 1-phthalimidoethoxy, 3-phthalimidopropoxy, 4-phthalimidobutoxy, 5-phthalimidopentyloxy, 6-phthalimidohexyloxy, and 1,1 -Dimethyl-2-phthalimidoethoxy, 2
A phthalimide-substituted alkoxy group in which the alkoxy moiety such as -methyl-3-phthalimidopropoxy group is a linear or branched alkoxy group having 1 to 6 carbon atoms can be exemplified.

Along with the nitrogen atom to which R ⁶ and R ⁷ are attached,
As a 5- to 6-membered saturated heterocyclic ring formed by bonding to each other with or without a nitrogen atom or an oxygen atom,
For example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino group and the like can be exemplified.

The above-mentioned heterocyclic group substituted by a group selected from the group consisting of piperidinyl group and lower alkyl group includes, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 4- (1-piperidino) piperidinyl, 2- (1 -Piperidino) pyrrolidinyl, 3- (1-
A group selected from the group consisting of a piperidinyl group such as piperidino) -4-methylpiperazinyl and a 3- (1-piperidino) morpholinyl group and a linear or branched alkyl group having 1 to 6 carbon atoms; The above-mentioned substituted heterocyclic group can be exemplified.

Examples of the phenyl lower alkanoyl group include phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl and 6-phenylhexanoyl. A phenylalkanoyl group which is a linear or branched alkanoyl group having 2 to 6 carbon atoms in the alkanoyl group portion such as a noyl group can be exemplified.

Examples of the cycloalkyl lower alkanoyl group include cyclohexylacetyl, 3-cyclopropylpropionyl, 2-cyclopentylpropionyl,
A straight or branched chain having 2 to 6 carbon atoms in an alkanoyl group such as cyclohexylbutyryl, 2,2-dimethyl-3-cycloheptylpropionyl, 5-cyclooctylpentanoyl, 6-cyclohexylhexanoyl, etc. Examples thereof include cycloalkylalkanoyl groups having 3 to 8 carbon atoms, which are alkanoyl groups.

Examples of the cycloalkylcarbonyl group include cycloalkylcarbonyl groups having 3 to 8 carbon atoms, such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl and the like.

Examples of the amino group which may have a lower alkanoyl group include amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino and the like. Carbon number 1
Examples of the amino group which may have from 6 to 6 linear or branched alkanoyl groups can be given.

Phenoxy lower alkanoyl which may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a lower alkoxy group as a substituent and an amino group which may have a lower alkanoyl group as a substituent on the phenyl ring. Examples of the group include phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyryl, 2,2-dimethyl-3-phenoxypropionyl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, (2-amino Phenoxy) acetyl,
3- (4-aminophenoxy) propionyl, (2-methylphenoxy) acetyl, (4-methylphenoxy)
Acetyl, (3-methylphenoxy) acetyl, (3-
(Methoxyphenoxy) acetyl, (3-acetylaminophenoxy) acetyl, 4- (2-propionylaminophenoxy) butyryl, 2,2-dimethyl-3- (4-
Butyrylaminophenoxy) propionyl, 5- (2-
Pentanoylaminophenoxy) pentanoyl, 6-
(4-hexanoylaminophenoxy) hexanoyl,
3- (2-ethylphenoxy) propionyl, 2- (4
-Propylphenoxy) propionyl, 4- (4-butylphenoxy) butyryl, 5- (3-pentylphenoxy) pentanoyl, 6- (4-hexylphenoxy) hexanoyl, (2,3-dimethylphenoxy) acetyl, (2,5 -Dimethylphenoxy) acetyl, (3,
4-dimethylphenoxy) acetyl, (3,4,5-trimethylphenoxy) acetyl, 3- (4-ethoxyphenoxy) propionyl, 2- (2-propoxyphenoxy) propionyl, 4- (3-butoxyphenoxy)
Butyryl, 5- (4-pentyloxyphenoxy) pentanoyl, 6- (4-hexyloxyphenoxy) hexanoyl, (3,4-dimethoxyphenoxy) acetyl, (3,5-dimethoxyphenoxy) acetyl,
(2,4-dimethoxyphenoxy) acetyl, (3,
4,5-trimethoxyphenoxy) acetyl, (2-acetylamino-4-methylphenoxy) acetyl, (4
-Acetylamino-3-methoxyphenoxy) a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent on a phenyl ring such as an acetyl group, a linear or branched alkoxy group having 1 to 6 carbon atoms The alkanoyl group portion which may have 1 to 3 groups selected from the group consisting of a group and an amino group which may have a linear or branched alkanoyl group having 1 to 6 carbon atoms has 2 to 6 carbon atoms; And a phenoxyalkanoyl group which is a linear or branched alkanoyl group.

Examples of the phthalimide-substituted lower alkanoyl group include 2-phthalimidoacetyl, 3-phthalimidopropionyl, 2-phthalimidopropionyl, 4-phthalimidobutyryl, 2,2-dimethyl-3-phthalimidopropionyl, 5-phthalimidopentanoyl, −
Alkanoyl groups such as phthalimidohexanoyl and 3-methyl-4-phthalimidobutyryl have 2 to 6 carbon atoms.
And a phthalimido-substituted alkanoyl group which is a linear or branched alkanoyl group.

The lower alkoxycarbonyl lower alkanoyl group includes, for example, methoxycarbonylacetyl, 3
-Methoxycarbonylpropionyl, ethoxycarbonylacetyl, 3-ethoxycarbonylpropionyl, 4
-Ethoxycarbonylbutyryl, 3-propoxycarbonylpropionyl, 2-methoxycarbonylpropionyl, 6-propoxycarbonylhexanol, 5-isopropoxycarbonylpentanor, 2,2-dimethyl-3
-Butoxycarbonylpropionyl, 2-methyl-3-
alkanoyl moieties such as tert-butoxycarbonylpropionyl, pentyloxycarbonylacetyl, hexyloxycarbonylacetyl and the like are straight-chain or branched-chain alkanoyl groups having 2 to 6 carbon atoms. Alkoxycarbonylalkanoyl groups. Examples of the carboxy lower alkanoyl group include carboxyacetyl, 3-carboxypropionyl, 2-carboxypropionyl, 4-carboxybutyryl, 2,2-dimethyl-3-carboxypropionyl, 5-carboxypentanoyl, and 6-carboxyhexanoyl Having 2 to 6 carbon atoms in the alkanoyl group moiety
And a carboxyalkanoyl group which is a linear or branched alkanoyl group.

Examples of the naphthyloxy lower alkanoyl group include naphthyloxyacetyl, 3-naphthyloxypropionyl, 2-naphthyloxypropionyl,
Straight-chain or branched having 2 to 6 carbon atoms in an alkanoyl group such as naphthyloxybutyryl, 2,2-dimethyl-3-naphthyloxypropionyl, 5-naphthyloxypentanoyl, and 6-naphthyloxyhexanoyl; A naphthyloxyalkanoyl group which is a chain alkanoyl group can be exemplified.

Examples of the phenyl lower alkoxycarbonyl group include benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenyl Hexyloxycarbonyl, 1,
1-dimethyl-2-phenylethoxycarbonyl, 2-
Examples thereof include a phenylalkoxycarbonyl group which is a straight-chain or branched-chain alkoxycarbonyl having 1 to 6 carbon atoms in an alkoxycarbonyl moiety such as a methyl-3-phenylpropoxycarbonyl group.

The lower alkyl group which may have a hydroxyl group as a substituent includes, in addition to the above-mentioned lower alkyl group,
Hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxyethyl, 4-hydroxybutyl, 3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5- Hydroxypentyl, 6-hydroxyhexyl, 2-methyl-3-hydroxypropyl, 2,3,4
A hydroxyl group as a substituent such as a trihydroxybutyl group;
Examples thereof include a linear or branched alkyl group having 1 to 6 carbon atoms, which may have 1 to 3 carbon atoms.

Examples of the phenyl lower alkyl group include benzyl, 2-phenylethyl, 1-phenylethyl,
The alkyl moiety such as 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, or 2-methyl-3-phenylpropyl has 1 to 6 carbon atoms. And a phenylalkyl group which is a linear or branched alkyl group.

Examples of the phenoxy lower alkyl group include phenoxymethyl, 1-phenoxyethyl, 2-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl and 1,1-dimethyl- 2-phenoxyethyl, 2
Phenoxyalkyl groups in which the alkyl moiety such as -methyl-3-phenoxypropyl group is a linear or branched alkyl group having 1 to 6 carbon atoms.

The phenyl group which may have 1 to 3 groups selected from the group consisting of a lower alkyl group, a lower alkoxy group and a halogen atom as a substituent on the phenyl ring includes, for example, phenyl, 2-methoxyphenyl, -Methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, , 4-Dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl, 2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,5-
Dimethoxyphenyl, 3,4-dipentyloxyphenyl, 3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,
-Fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 3,5-
Dibromophenyl, 3,4,5-trichlorophenyl,
2-methoxy-3-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl,
4-pentylphenyl, 4-hexylphenyl, 3,4
-Dimethylphenyl, 3,4-diethylphenyl, 2,
4-dimethylphenyl, 2,5-dimethylphenyl,
2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 3-chloro-4-methylphenyl, 3-methoxy-4-methyl-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl, A linear or branched alkyl group having 1 to 6 carbon atoms as a substituent on a phenyl ring such as a 5,5-diiodo-4-methoxyphenyl group;
And a phenyl group which may have 1 to 3 groups selected from the group consisting of a straight-chain or branched alkoxy group and a halogen atom.

The amino lower alkyl group which may have a lower alkyl group as a substituent includes aminomethyl,
2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl,
2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethyl Aminomethyl, (N-ethyl-N-propylamino) methyl, 2- (N-methyl-N
-Hexylamino) ethyl as a substituent having 1 carbon atom
Examples thereof include a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms and having an amino group which may have 1 to 2 straight-chain or branched-chain alkyl groups.

Together with the nitrogen atom to which R ⁹ and R ¹⁰ are attached,
Examples of the 5- to 6-membered saturated heterocyclic ring formed by bonding to each other via a nitrogen atom or an oxygen atom or not via a nitrogen atom or an oxygen atom include a pyrrolidinyl, piperidinyl, piperazinyl, morpholino group and the like.

The above-mentioned heterocyclic group substituted by a group selected from the group consisting of a lower alkyl group, a lower alkoxycarbonyl group and a piperidinyl group includes, in addition to the heterocyclic ring substituted by a lower alkyl group or a piperidinyl group, 4-methoxy Carbonylpiperazinyl, 4-ethoxycarbonylpiperidinyl, 2-propoxycarbonylpyrrolidinyl, 2-
A straight or branched chain having 1 to 6 carbon atoms such as pentyloxycarbonylmorpholino, 4-hexyloxycarbonylpiperidinyl, 4-ethoxycarbonyl-3-methylpiperidinyl, and 3-methyl-4-ethoxycarbonylpiperazinyl group. Examples of the above-mentioned heterocyclic group in which 1 to 3 groups selected from the group consisting of a branched alkyl group, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms and a piperidinyl group are substituted.

Along with the nitrogen atom to which R ¹⁴ and R ¹⁵ are attached,
Examples of the 5- or 6-membered saturated heterocyclic ring formed by bonding to each other via a nitrogen atom or an oxygen atom or not through the nitrogen atom or the oxygen atom include, for example, pyrrolidinyl, piperidinyl, piperazinyl,
Examples include a morpholino group.

The above heterocyclic group substituted by a lower alkyl group includes 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 2-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,4 5-trimethylpiperidinyl, 4
-Butylpiperidinyl, 3-pentylmorpholino, 4-
The above-mentioned heterocyclic group in which 1 to 6 linear or branched alkyl groups having 1 to 6 carbon atoms such as hexylpiperazinyl group are substituted by 1 to 3 groups can be exemplified.

Examples of the heterocycle of the general formula (1) include tetrahydroquinolyl, 2,3,4,5-tetrahydro-
1H-benzoazepinyl, 1,2,3,4,5,6-hexahydrobenzazocinyl, 1,2-dihydroquinolyl, 2,3-dihydro-1H-benzoazepinyl,
Heterocycles such as a 2,3,4-tetrahydrobenzazosinyl group can be exemplified.

The group — (CH ₂ ) _p — or the group —CH ＝ C
H- (CH _{2) q} - carbon atoms in an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group or a group -NR ¹³ -
(R ¹³ represents a hydrogen atom or a lower alkyl group.) As the heterocyclic ring of the general formula (1), for example, 3,4-
Dihydro-2H-1,4-benzoxazinyl, 1,
2,3,5-tetrahydro-4,1-benzoxazepinyl, 1,2,3,4-tetrahydroquinoxalinyl,
1,2,3,4,5,6-hexahydro-1,5-benzodiazosinyl, 5-methyl-1,2,3,4,5,6
-Hexahydro-1,5-benzodiazosinyl, 4-methyl-1,2,3,4-tetrahydroquinoxalinyl,
1,2,3,4-tetrahydro-5,1-benzoxazepinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 2,3,4,5-tetrahydro-1,5-benzothia Zepinyl, 1,2,3,5-tetrahydro-
4,1-benzothiazepinyl, 4-ethyl-1,2,2
3,4-tetrahydroquinoxalinyl, 4-propyl-
1,2,3,4-tetrahydroquinoxalinyl, 4-butyl-1,2,3,4-tetrahydroquinoxalinyl,
4-pentyl-1,2,3,4-tetrahydroquinoxalinyl, 4-hexyl-1,2,3,4-tetrahydroquinoxalinyl, 2,3,4,5-tetrahydro-1H
-1,4-benzodiazepinyl, 4-methyl-2,3
4,5-tetrahydro-1H-1,4-benzodiazepinyl, 4-ethyl-2,3,4,5-tetrahydro-1
H-1,4-benzodiazepinyl, 4-propyl-2,
3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 4-butyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 4-pentyl-
2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 4-hexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl, 2,3
4,5-tetrahydro-1H-1,5-benzodiazepinyl, 5-methyl-2,3,4,5-tetrahydro-1
H-1,5-benzodiazepinyl, 5-ethyl-2,
3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 5-propyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 5-butyl-
2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 5-pentyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl, 5-hexyl- 2,3,4,5-tetrahydro-1H-1,5-
Benzodiazepinyl, 3,4-dihydro-1-oxo-
2H-1,4-benzothiazepinyl, 3,4-dihydro-1,1-dioxo-2H-1,4-benzothiazepinyl, 1-oxo-2,3,4,5-tetrahydro-1,
5-benzothiazepinyl, 1,1-dioxo-2,3,
4,5-tetrahydro-1,5-benzothiazepinyl,
4-oxo-1,2,3,5-tetrahydro-4,1-
Benzothiazepinyl, 4,4-dioxo-1,2,3
5-tetrahydro-4,1-above group such as benzothiazolium benzindolyl group - (CH _{2) p} - or a group -CH = CH- (C
H ₂ ) The carbon atom in _q − is an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group or a group —NR ¹³ — (R ¹³ is a hydrogen atom or a linear or branched alkyl group having 1 to 6 carbon atoms. Heterocycles which are shown in the following examples) can be exemplified.

As the halogen-substituted lower alkoxy group,
For example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4
Carbon number having 1 to 3 halogen atoms such as trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, and 5,6-dichlorohexyloxy group Examples include 1 to 6 straight-chain or branched alkoxy groups.

Examples of the halogen-substituted lower alkanoyl group include 2,2,2-trifluoroacetyl and 2,2,2-
Trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,
3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl,
Examples of substituents such as 6-bromohexanoyl and 5,6-dibromohexanoyl groups include straight-chain or branched alkanoyl groups having 1 to 6 carbon atoms and having 1 to 3 halogen atoms.

Examples of the aminocarbonyl having a lower alkyl group as a substituent include lower amino groups such as methylaminocarbonylmethoxy, 1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy, 3-isopropylaminocarbonylpropoxy and 4-butylaminocarbonyl. Butoxy, 5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy, dimethylaminocarbonylmethoxy, 3-
Straight chain having 1 to 6 carbon atoms as a substituent such as diethylaminocarbonylpropoxy, diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino) carbonylmethoxy, or 2- (N-methyl-N-hexylamino) carbonylethoxy; A straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms and having an aminocarbonyl group having 1 to 2 branched-chain alkyl groups can be exemplified.

Examples of the carbamoyl lower alkyl group include carbamoylmethyl, 2-carbamoylethyl,
Carbamoylethyl, 3-carbamoylpropyl, 4
Carbamoylbutyl, 5-carbamoylpentyl, 6
A carbamoylalkyl group in which the alkyl portion such as a carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl, or 2-methyl-3-carbamoylpropyl group is a linear or branched alkyl group having 1 to 6 carbon atoms; Can be illustrated.

Examples of the amino lower alkanoyl group which may have a lower alkyl group as a substituent include 2-aminoacetyl, 3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl and 6-aminohexayl. Noyl, 2,2-dimethyl-3-
Aminopropionyl, 2-methyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2
1-carbon group as a substituent such as -diethylaminoacetyl, 2- (N-ethyl-N-propylamino) acetyl, 3- (N-methyl-N-hexylamino) propionyl group or the like.
Examples thereof include a linear or branched alkanoyl group having 2 to 6 carbon atoms and having an amino group which may have 1 to 6 linear or branched alkyl groups.

The amino lower alkyl group which may have a lower alkanoyl group as a substituent includes, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl,
Aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl, 1-acetylaminoethyl, 2- As a substituent such as propionylaminoethyl, 3-isopropionylaminopropyl, 4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl, or formylaminomethyl group, a straight-chain having 1 to 6 carbon atoms or Examples thereof include a linear or branched alkyl group having 1 to 6 carbon atoms and an amino group which may have a branched alkanoyl group.

The anilinocarbonyl group which may have a lower alkyl group as a substituent on the phenyl ring includes:
For example, anilinocarbonyl, 2-methylanilinocarbonyl, 3-methylanilinocarbonyl, 4-methylanilinocarbonyl, 2-ethylanilinocarbonyl, 3-
Ethylanilinocarbonyl, 4-ethylanilinocarbonyl, 4-isopropylanilinocarbonyl, 3-butylanilinocarbonyl, 4-pentylanilinocarbonyl, 4-hexylanilinocarbonyl, 3,4-dimethylanilinocarbonyl, 3 , 4-Diethylanilinocarbonyl, 2,4-dimethylanilinocarbonyl, 2,5
1 to 6 carbon atoms as a substituent on a phenyl ring such as -dimethylanilinocarbonyl, 2,6-dimethylanilinocarbonyl, 3,4,5-trimethylanilinocarbonyl, etc.
Anilinocarbonyl group which may have 1 to 3 linear or branched alkyl groups.

The phenylsulfonyl group which may have a substituent selected from the group consisting of a halogen atom and a lower alkyl group on the phenyl ring includes, for example, phenylsulfonyl, 2-chlorophenylsulfonyl, 3-chlorophenylsulfonyl, Chlorophenylsulfonyl, 2-fluorophenylsulfonyl, 3-fluorophenylsulfonyl, 4-fluorophenylsulfonyl,
2-bromophenylsulfonyl, 3-bromophenylsulfonyl, 4-bromophenylsulfonyl, 2-iodophenylsulfonyl, 3-iodophenylsulfonyl,
4-iodophenylsulfonyl, 3,4-dichlorophenylsulfonyl, 3,5-dichlorophenylsulfonyl, 2,6-dichlorophenylsulfonyl, 2,3-dichlorophenylsulfonyl, 2,4-dichlorophenylsulfonyl, 3,4-difluorophenylsulfonyl,
3,5-dibromophenylsulfonyl, 3,4,5-trichlorophenylsulfonyl, 2-ethyl-3-chlorophenylsulfonyl, 2-methylphenylsulfonyl,
3-methylphenylsulfonyl, 4-methylphenylsulfonyl, 2-ethylphenylsulfonyl, 3-ethylphenylsulfonyl, 4-ethylphenylsulfonyl,
4-isopropylphenylsulfonyl, 3-butylphenylsulfonyl, 4-pentylphenylsulfonyl, 4
-Hexylphenylsulfonyl, 3,4-dimethylphenylsulfonyl, 3,4-diethylphenylsulfonyl, 2,4-dimethylphenylsulfonyl, 2,5-dimethylphenylsulfonyl, 2,6-dimethylphenylsulfonyl, 2,4,6 -Trimethylphenylsulfonyl, 3,4,5-trimethylphenylsulfonyl, 3-
Chloro-4-methylphenylsulfonyl, 4-methyl-
5-iodophenylsulfonyl, 3,4-dimethyl-5
-Bromophenylsulfonyl, 3,5-diiodo-4-
A phenylsulfonyl group which may have 1 to 3 carbon atoms as a substituent on a phenyl ring such as a methylphenylsulfonyl group, which may have 1 to 6 groups selected from the group consisting of a linear or branched alkyl group and a halogen atom. Can be exemplified.

Examples of the phthalimide-substituted lower alkyl group include phthalimidomethyl, 2-phthalimidoethyl, 1-phthalimidoethyl, 3-phthalimidopropyl, 4-phthalimidobutyl, 5-phthalimidopentyl, 6-phthalimidohexyl and 1,1-dimethyl -2
A phthalimidoalkyl group in which the alkyl portion such as -phthalimidoethyl or 2-methyl-3-phthalimidopropyl group is a linear or branched alkyl group having 1 to 6 carbon atoms can be given. Examples of the lower alkynyl group include ethynyl, 2-propynyl, 2-butynyl, 3-butynyl,
Examples thereof include a linear or branched alkynyl group having 2 to 6 carbon atoms such as -methyl-2-propynyl, 2-pentynyl, and 2-hexynyl group.

The benzoyl group which may have a halogen atom as a substituent on the phenyl ring includes, for example, benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl,
3-fluorobenzoyl, 4-fluorobenzoyl, 2
-Bromobenzoyl, 3-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzoyl, 3,4-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,6-dichlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-
Dichlorobenzoyl, 3,4-difluorobenzoyl,
A benzoyl group which may have 1 to 3 halogen atoms as a substituent on a phenyl ring such as a 3,5-dibromobenzoyl group or a 3,4,5-trichlorobenzoyl group can be exemplified.

Examples of the phenyl lower alkoxy group include benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1- Examples thereof include a phenylalkoxy group which is a straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms in the alkoxy moiety such as dimethyl-2-phenylethoxy and 2-methyl-3-phenylpropoxy groups.

Examples of the amino-lower alkoxy group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include aminomethoxy, 2-aminoethoxy, 1-aminoethoxy and 3-aminopropoxy. , 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy, 1-acetylaminoethoxy, 2- Propionylaminoethoxy, 3-isopropionylaminopropoxy, 4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy, 6
-Hexanoylaminohexyloxy, formylaminomethoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-
Pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, (N-ethyl-N-propylamino) methoxy, 2- (N-methyl-
As a substituent such as an (N-hexylamino) ethoxy group or the like, a linear or branched alkyl group having 1 to 6 carbon atoms and 1 to 6 carbon atoms
A straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms and having an amino group which may have 1 to 2 groups selected from the group consisting of 6 straight-chain or branched-chain alkanoyl groups can be exemplified.

The benzoyloxy group which may have a halogen atom as a substituent on the phenyl ring includes, for example, benzoyloxy, 2-chlorobenzoyloxy, 3
-Chlorobenzoyloxy, 4-chlorobenzoyloxy, 2-fluorobenzoyloxy, 3-fluorobenzoyloxy, 4-fluorobenzoyloxy, 2-bromobenzoyloxy, 3-bromobenzoyloxy,
4-bromobenzoyloxy, 2-iodobenzoyloxy, 3-iodobenzoyloxy, 4-iodobenzoyloxy, 3,4-dichlorobenzoyloxy, 3,
5-dichlorobenzoyloxy, 2,6-dichlorobenzoyloxy, 2,3-dichlorobenzoyloxy,
1 to 3 halogen atoms as substituents on the phenyl ring such as 2,4-dichlorobenzoyloxy, 3,4-difluorobenzoyloxy, 3,5-dibromobenzoyloxy, and 3,4,5-trichlorobenzoyloxy groups A benzoyloxy group which may be present can be exemplified.

The lower alkanoyloxy-substituted lower alkyl group includes, for example, acetyloxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl,
Acetyloxypropyl, 4-acetyloxybutyl,
4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-acetyloxyhexyl, 6-tert-
Butylcarbonyloxyhexyl, 1,1-dimethyl-
C2-C6 linear or branched alkanoyloxy group such as 2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl group, etc. Substituted C1-C6 linear or branched alkyl Groups can be exemplified.

The lower alkylsulfonyloxy lower alkyl group includes, for example, methylsulfonyloxymethyl,
1-ethylsulfonyloxyethyl, 2-propylsulfonyloxyethyl, 3-isopropylsulfonyloxypropyl, 4-butylsulfonyloxybutyl, 5-
A linear or branched chain having 1 to 6 carbon atoms such as pentylsulfonyloxypentyl, 6-hexylsulfonyloxyhexyl, 1,1-dimethyl-2-methylsulfonyloxyethyl, and 2-methyl-3-ethylsulfonyloxypropyl group Linear or branched alkyl group having 1 to 6 carbon atoms, which can be substituted with an alkylsulfonyloxy group.

Examples of the azido lower alkyl group include azidomethyl, 1-azidoethyl, 2-azidoethyl,
Azido-substituted straight-chain having 1 to 6 carbon atoms, such as -azidopropyl, 4-azidobutyl, 5-azidopentyl, 6-azidohexyl, 1,1-dimethyl-2-azidoethyl, 2-methyl-3-azidopropyl and the like; A branched alkyl group can be exemplified.

The lower alkanoyloxyimino group includes, for example, formyloxyimino, acetyloxyimino, propionyloxyimino, butyryloxyimino, isobutyryloxyimino, pentanoyloxyimino, tert-butylcarbonyloxyimino, hexanoyloxy Examples thereof include a straight or branched alkanoyloxyimino group having 1 to 6 carbon atoms such as an imino group.

Examples of the lower alkylidene group include straight-chain or branched-chain alkylidene groups having 1 to 6 carbon atoms such as methylidene, ethylidene, propylidene, isopropylidene, butylidene, hexylidene and the like.

Examples of the oxiranyl-substituted lower alkyl group include oxiranylmethyl, 1-oxiranylethyl, 2-oxiranylethyl, 3-oxiranylpropyl, 4-oxiranylbutyl, and 5-oxiranyl Pentyl, 6-oxiranylhexyl, 1,1-dimethyl-2
Oxylanyl groups such as -oxiranylethyl and 2-methyl-3-oxiranylpropyl groups may be substituted by straight-chain or branched-chain alkyl groups having 1 to 6 carbon atoms.

Examples of the lower alkyl group having one or two groups selected from the group consisting of a lower alkoxy group as a substituent, a hydroxyl group and an amino group which may have a lower alkyl group as a substituent include methoxymethyl, 1- Ethoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-
2-methoxyethyl, 2-methyl-3-ethoxypropyl, 3-methoxy-2-hydroxypropyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxyethyl, 4- Hydroxybutyl, 3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,
6-dihydroxyhexyl, 5-hydroxypentyl,
6-hydroxyhexyl, 6- (N-ethyl-N-methylamino) -5-methoxyhexyl, 2-methyl-3-
Hydroxypropyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,
1,1-dimethyl-2-aminoethyl, 2-methyl-3
-Aminopropyl, methylaminomethyl, ethylaminomethyl, propylaminomethyl, isopropylaminomethyl, butylaminomethyl, tert-butylaminomethyl, pentylaminomethyl, hexylaminomethyl, dimethylaminomethyl, diethylaminomethyl, dipropylaminomethyl, Dibutylaminomethyl, dipentylaminomethyl, dihexylaminomethyl, N-methyl-N
-Ethylaminomethyl, N-methyl-N-propylaminomethyl, N-methyl-N-butylaminomethyl, N-
Methyl-N-hexylaminomethyl, 1-methylaminoethyl, 2-ethylaminoethyl, 3-propylaminopropyl, 4-butylaminobutyl, 1,1-dimethyl-2-pentylaminoethyl, 5-hexylaminopentyl, 6-dimethylaminohexyl, 4-dimethylaminobutyl, 2-diethylaminoethyl, 1- (N-methyl-N-hexylamino) ethyl, 3-dihexylaminopropyl, 6-diethylaminohexyl, 4-dibutylaminobutyl, (N-methyl-N-pentylamino) ethyl, 2-hydroxy-3-diethylaminopropyl, 3-hydroxy-4-methylaminobutyl, 5-
Hydroxy-6-diethylaminohexyl, 4-hydroxy-5-dimethylaminopentyl, 4-hydroxy-
As a substituent such as 5-methylaminopentyl, 4-hydroxy-5-diethylaminopentyl, 5-hydroxy-6-ethylaminohexyl, 5-hydroxy-6-isopropylaminohexyl, or 5-hydroxy-6-aminohexyl, A group selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms, a hydroxyl group and an amino group which may have a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent. Examples thereof include a linear or branched alkyl group having 1 to 2 carbon atoms and 1 to 6 carbon atoms.

The aminocarbonyloxy group which may have a lower alkyl group as a substituent includes, for example, aminocarbonyloxy, methylaminocarbonyloxy,
Ethylaminocarbonyloxy, propylaminocarbonyloxy, isopropylaminocarbonyloxy, butylaminocarbonyloxy, tert-butylaminocarbonyloxy, pentylaminocarbonyloxy, hexylaminocarbonyloxy, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, dipropylaminocarbonyl Oxy, dibutylaminocarbonyloxy, dipentylaminocarbonyloxy, dihexylaminocarbonyloxy, N-methyl-N-ethylaminocarbonyloxy, N-ethyl-N-propylaminocarbonyloxy, N-methyl-N-butylaminocarbonyloxy, A linear or branched alkyl having 1 to 6 carbon atoms as a substituent such as an N-methyl-N-hexylaminocarbonyloxy group; An aminocarbonyloxy group which may have 1 to 2 groups can be exemplified.

The lower alkanoyloxy group which may have a halogen atom as a substituent includes, for example, 2,2,2-trifluoroacetyloxy and 2,2,2-trichloroacetyloxy in addition to the lower alkanoyloxy group. , 2-chloroacetyloxy, 2-bromoacetyloxy, 2-fluoroacetyloxy, 2-iodoacetyloxy, 2,2-difluoroacetyloxy,
2,2-dibromoacetyloxy, 3,3,3-trifluoropropionyloxy, 3,3,3-trichloropropionyloxy, 3-chloropropionyloxy,
2,3-dichloropropionyloxy, 4,4,4-trichlorobutyryloxy, 4-fluorobutyryloxy, 5-chloropentanoyloxy, 3-chloro-2-
A linear or branched alkanoyl having 1 to 6 carbon atoms, which may have 1 to 3 halogen atoms as a substituent such as methylpropionyloxy, 6-bromohexanoyloxy, 5,6-dibromohexanoyloxy, etc. Groups can be mentioned.

Examples of the amino lower alkyl group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent include, for example, aminomethyl,
-Aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutoxy, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl,
2-methyl-3-aminopropyl, acetylaminomethyl, 1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl, 4-
Butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl, formylaminomethyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl , 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, (N-ethyl-N-propylamino) methyl, 2- (N-methyl-N-hexylamino) ethyl and the like. A carbon having an amino group which may have one or two groups selected from the group consisting of a straight-chain or branched alkyl group having 1 to 6 carbon atoms and a straight-chain or branched alkanoyl group having 1 to 6 carbon atoms; Examples include straight-chain or branched-chain alkyl groups of the formulas 1 to 6.

The amino-lower alkanoyloxy group which may have a lower alkyl group as a substituent includes 2-amino
Aminoacetyloxy, 3-aminopropionyloxy, 2-aminopropionyloxy, 4-aminobutyryloxy, 5-aminopentanoyloxy, 6-aminohexanoyloxy, 2,2-dimethyl-3-aminopropionyloxy, 2 -Methyl-3-aminopropionyloxy, 2-methylaminoacetyloxy, 2-ethylaminopropionyloxy, 3-propylaminopropionyloxy, 3-isopropylaminopropionyloxy, 4-butylaminobutyryloxy, 5-pentylaminopenta Noyloxy, 6-hexylaminohexanoyloxy, 2-dimethylaminoacetyloxy,
A straight-chain having 1 to 6 carbon atoms as a substituent such as 2-diethylaminoacetyloxy, 2- (N-ethyl-N-propylamino) acetyloxy, 3- (N-methyl-N-hexylamino) propionyloxy; Examples thereof include a straight or branched alkanoyloxy group having 2 to 6 carbon atoms and having an amino group which may have 1 to 2 branched alkyl groups.

Examples of the pyridyl lower alkyl group include (4-pyridyl) methyl, 1- (3-pyridyl) ethyl, 2- (2-pyridyl) ethyl, 3- (2-pyridyl) propyl and 4- (3- Pyridyl) butyl, 5- (4
-Pyridyl) pentyl, 6- (2-pyridyl) hexyl, 1,1-dimethyl-2- (3-pyridyl) ethyl,
Examples thereof include a pyridylalkyl group in which an alkyl moiety such as a 2-methyl-3- (4-pyridyl) propyl group is a linear or branched alkyl group having 1 to 6 carbon atoms.

Examples of the 5- or 6-membered saturated heterocyclic group formed by R ¹⁸ and R ¹⁹ which are bonded to each other via a nitrogen atom, an oxygen atom or a sulfur atom together with or without a bonding nitrogen atom include, for example, Pyrrolidinyl, piperidinyl,
Examples include piperazinyl, morpholino, and thiomorpholino groups.

The heterocyclic group substituted by an oxo group, a lower alkyl group, a lower alkanoyl group or a carbamoyl group includes, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 2-methylthiomorpholino, 4-acetylpiperazinyl, 2 -Propanoylmorpholino, 3-butyrylthiomorpholino, 3-pentanoylpyrrolidinyl, 4-hexanoylpiperidinyl, 3
-Methyl-4-acetylpiperazinyl, 2-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl, 3-
Oxo groups such as carbamoylthiomorpholino, 2-carbamoylmorpholino, 3-carbamoylpiperidinyl, 1-oxothiomorpholino, and 1,1-dioxothiomorpholino, straight-chain or branched alkyl having 1 to 6 carbon atoms Group,
The above-mentioned heterocyclic group in which 1 to 3 carbon atoms are substituted with 1 to 3 straight or branched alkanoyl groups or carbamoyl groups.

The lower alkylsulfonyl group includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl,
Examples thereof include linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms such as tert-butylsulfonyl, pentylsulfonyl, and hexylsulfonyl groups.

Examples of the aminocarbonyl group which may have a lower alkyl group as a substituent include, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, Pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylamino Carbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, etc. Examples thereof include an aminocarbonyl group which may have 1 to 2 straight-chain or branched alkyl groups.

Examples of the cyano-substituted lower alkyl group include cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-
Examples thereof include a cyanoalkyl group in which the alkyl portion such as a 2-cyanoethyl or 2-methyl-3-cyanopropyl group is a linear or branched alkyl group having 1 to 6 carbon atoms.

The lower alkoxycarbonyl-substituted lower alkyl group includes, for example, methoxycarbonylmethyl, 3
-Methoxycarbonylpropyl, ethoxycarbonylmethyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-
Alkoxycarbonyl moieties such as 3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, etc. are straight-chain or branched-chain alkoxycarbonyl groups having 1 to 6 carbon atoms. A straight-chain or branched alkoxycarbonylalkyl group can be mentioned.

As the carboxy-substituted lower alkyl group,
For example, carboxymethyl, 2-carboxyethyl, 1-
Carbon number of the alkyl moiety such as carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, etc. Is a carboxyalkyl group having 1 to 6 linear or branched alkyl groups.

The tetrahydropyranyloxy-substituted lower alkyl group includes, for example, (2-tetrahydropyranyl)
Oxymethyl, 2- (3-tetrahydropyranyl) oxyethyl, 1- (4-tetrahydropyranyl) oxyethyl, 3- (2-tetrahydropyranyl) oxypropyl, 4- (3-tetrahydropyranyl) oxybutyl,
5- (4-tetrahydropyranyl) oxypentyl, 6
-(2-tetrahydropyranyl) oxyhexyl, 1,
An alkyl moiety such as a 1-dimethyl-2- (3-tetrahydropyranyl) oxyethyl or 2-methyl-3- (4-tetrahydropyranyl) oxypropyl group has 1 to 1 carbon atoms.
And a tetrahydropyranyloxy-substituted alkyl group which is a straight or branched alkyl group of No. 6.

The piperidinyl group which may have a phenyl lower alkyl group as a substituent on the piperidine ring includes piperidinyl, 1-benzyl-4-piperidinyl,
1- (2-phenylethyl) -3-piperidinyl, 1-
(1-phenylethyl) -2-piperidinyl, 1- (3
-Phenylpropyl) -4-piperidinyl, 1- (4-
Phenylbutyl) -4-piperidinyl, 1- (5-phenylpentyl) -4-piperidinyl, 1- (6-phenylhexyl) -4-piperidinyl, 1- (1,1-dimethyl-2-phenylethyl) -3 -Piperidinyl, 1-
(2-methyl-3-phenylpropyl) -2-piperidinyl group or the like has a phenylalkyl group as a substituent on the piperidine ring, which is a linear or branched alkyl group having 1 to 6 carbon atoms in the alkyl portion. Examples include a piperidinyl group which may be present.

Examples of the imidazolyl-substituted lower alkanoyl group include (1-imidazolyl) acetyl and 3- (2
-Imidazolyl) propionyl, 2- (4-imidazolyl) propionyl, 4- (1-imidazolyl) butyryl, 2,2-dimethyl-3- (2-imidazolyl) propionyl, 5- (4-imidazolyl) pentanoyl, 6
An imidazolylalkanoyl group which is a straight or branched alkanoyl group having 2 to 6 carbon atoms in the alkanoyl group portion such as-(1-imidazolyl) hexanoyl group can be mentioned.

The amino-lower alkanoyl group which may have a group selected from the group consisting of a lower alkyl group and a lower alkoxycarbonyl group as a substituent includes, for example, 2-
Aminoacetyl, 3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl, 2,2-dimethyl-
3-aminopropionyl, 2-methyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3
-Isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethylaminoacetyl, 2- (N-ethyl-
N-propylamino) acetyl, 3- (N-methyl-N
-Hexylamino) propionyl, 2-methoxycarbonylaminoacetyl, 2-ethoxycarbonylaminoacetyl, 3-propoxycarbonylaminopropionyl, 4-butoxycarbonylaminobutyryl, 2-tert
-Butoxycarbonylaminoacetyl, 5-pentyloxycarbonylaminopentanoyl, 6-hexyloxycarbonylaminohexanoyl, 2- (N-methyl-
(N-tert-butoxycarbonylamino) acetyl group or the like as a substituent such as a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms and a straight-chain or branched-chain alkoxycarbonyl group having 1 to 6 carbon atoms. Examples thereof include a linear or branched alkanoyl group having 2 to 6 amino-substituted carbon atoms which may have 1 to 2 selected groups.

Examples of the aminocarbonyl lower alkyl group having a lower alkyl group as a substituent include, for example, methylaminocarbonylmethyl, 1-ethylaminocarbonylethyl, 2-propylaminocarbonylethyl, 3-isopropylaminocarbonylpropyl, 4-butylamino Carbonylbutyl, 5-pentylaminocarbonylpentyl, 6-hexylaminocarbonylhexyl, dimethylaminocarbonylmethyl, 3-diethylaminocarbonylpropyl, diethylaminocarbonylmethyl, (N
-Ethyl-N-propylamino) carbonylmethyl, 2
1 to 6 carbon atoms having an aminocarbonyl group having 1 to 2 linear or branched alkyl groups having 1 to 6 carbon atoms as a substituent such as-(N-methyl-N-hexylamino) carbonylethyl group; Or a straight-chain or branched-chain alkyl group.

Examples of the amino-substituted lower alkoxy group which may have a lower alkyl group as a substituent include, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, and 5-aminobutoxy.
Aminopentyloxy, 6-aminohexyloxy,
1,1-dimethyl-2-aminoethoxy, 2-methyl-
3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3
-Isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy,
(N-methyl-N-propylamino) methoxy, 2-
(N-methyl-N-hexylamino) ethoxy having 1 to 2 carbon atoms having an amino group which may have 1 to 2 linear or branched alkyl groups having 1 to 6 carbon atoms as a substituent.
And 6 straight-chain or branched alkoxy groups.

The compounds of the present invention can be easily prepared, for example, by the methods described in EP 450,097.

Among the compounds (1) used as the active ingredient in the present invention, the compound having an acidic group can form a salt with a pharmacologically acceptable basic compound. Examples of such a basic compound include metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide, alkali metal carbonates and bicarbonates such as sodium carbonate and sodium hydrogen carbonate, and sodium methylate. And alkali metal alcoholates such as potassium ethylate. Further, in the compound (1) as an active ingredient in the present invention, a compound having basicity can easily form a salt with a usual pharmacologically acceptable acid. Examples of such an acid include inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, and hydrobromic acid, acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, and benzoic acid. And the like. These salts can also be used as the active ingredient compound in the present invention, similarly to the compound (1) in the free form. The compound (1)
Include stereoisomers and optical isomers, and these can be similarly used as the active ingredient compound.

The compound of the present invention obtained by the method described in the above-mentioned European Patent No. 4,500,977 can be separated from the reaction system by a conventional separation means and further purified. As the separation and purification means, for example, a distillation method, a recrystallization method, a column chromatography, an ion exchange chromatography, a gel chromatography, an affinity chromatography, a preparative thin layer chromatography, a solvent extraction method and the like can be adopted.

The thus obtained active ingredient compound of the present invention is effective as an oxytocin antagonist, and the antagonist is used in the form of a general pharmaceutical preparation. Formulations include commonly used fillers, extenders, binders, humectants, disintegrants,
It is prepared using a diluent or excipient such as a surfactant or a lubricant. Various forms can be selected as the pharmaceutical preparation depending on the purpose of treatment, and typical examples are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules,
Suppositories, injections (solutions, suspensions, etc.) and the like can be mentioned. In molding into tablets, various carriers well-known in the art can be widely used as carriers. Examples thereof include lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, excipients such as silicic acid,
Binders such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, dried starch,
Disintegrants such as sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, sucrose, stearin, cocoa butter, hydrogenated oil Disintegration inhibitors such as quaternary ammonium bases, absorption promoters such as sodium lauryl sulfate, humectants such as glycerin and starch, starch, lactose, kaolin, bentonite,
Adsorbents such as colloidal silicic acid, lubricating agents such as purified talc, stearates, powdered boric acid, and polyethylene glycol can be used. Further tablets are tablets coated with a usual coating as necessary, such as sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets,
It can be a film-coated tablet, a double tablet, or a multilayer tablet. In molding into the form of pills, a wide variety of carriers conventionally known in this field can be used. Examples thereof include excipients such as glucose, lactose, starch, cocoa butter, hardened vegetable oils, kaolin, talc, binders such as gum arabic, tragacanth, gelatin, ethanol, disintegrants such as laminaran, agar, etc. Can be used. In the case of molding into a suppository form, conventionally known carriers can be widely used. Examples include polyethylene glycol, cocoa butter, higher alcohols,
Esters of higher alcohols, gelatin, semi-synthetic glycerides and the like can be mentioned. Capsules are prepared according to a conventional method, usually by mixing the active ingredient compound with the various carriers exemplified above and filling the mixture into hard gelatin capsules, soft capsules and the like. When prepared as an injection, liquid preparations, emulsions and suspensions are preferably sterilized and isotonic with blood, and are commonly used as diluents in the art when molded into these forms. And water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, a sufficient amount of salt, glucose or glycerin to prepare an isotonic solution may be included in the pharmaceutical preparation, and a usual solubilizer, buffer, soothing agent, etc. may be added. You may. Coloring agent if necessary,
Preservatives, flavors, flavors, sweeteners, and other pharmaceuticals can also be included in the pharmaceutical formulation.

The amount of the active ingredient compound to be contained in the oxytocin antagonist of the present invention is not particularly limited and may be appropriately selected from a wide range.
70% by weight, preferably about 5 to 50% by weight.

The method of administration of the oxytocin antagonist of the present invention is not particularly limited, and is administered according to various preparation forms, age, sex and other conditions of the patient, degree of disease, and the like. For example, tablets, pills, solutions, suspensions, emulsions, granules, and capsules are orally administered. In the case of an injection, it is administered alone or mixed with a normal replenisher such as glucose and amino acids, and administered intravenously.
It is administered intradermally, subcutaneously or intraperitoneally. In the case of suppositories, they are administered rectally.

The dose of the oxytocin antagonist of the present invention is appropriately selected depending on the usage, the age of the patient, sex and other conditions, the degree of the disease, and the like. It is good to be about 0.6 to 50 mg. It is desirable that the active ingredient compound is contained in the dosage unit form in a range of about 10 to 1000 mg.

[0100]

EXAMPLES In order to explain the present invention in more detail, examples of the preparation of the oxytocin antagonist of the present invention will be given, followed by examples of the production of the above-mentioned active ingredient compounds, and test examples of the active ingredient compounds. .

Formulation Example 1 4-methylamino-1- [4- (3,5-dichlorobenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 150 g Avicel (trade name, manufactured by Asahi Kasei Corporation) 40 g corn starch 30 g magnesium stearate 2 g hydroxypropyl methylcellulose 10 g polyethylene glycol-6000 3 g castor oil 40 g ethanol 40 g After mixing and polishing the active ingredient of the present invention, Avicel, corn starch and magnesium stearate, sugar coating R10 mm
Tablet with kine. The obtained tablets were treated with hydroxypropyl methylcellulose, polyethylene glycol-600.
0, coating with a film coating agent consisting of castor oil and ethanol to produce film-coated tablets.

Formulation Example 2 1- [4- (N-butylanilinoacetylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 150 g citric acid 1.0 g lactose 33.5 g phosphoric acid Dicalcium 70.0 g Pluronic F-68 30.0 g Sodium lauryl sulfate 15.0 g Polyvinyl pyrrolidone 15.0 g Polyethylene glycol (Carbowax 1500) 4.5 g Polyethylene glycol (Carbowax 6000) 45.0 g Corn starch 30.0 g Dry stearic acid Sodium 3.0 g Dry magnesium stearate 3.0 g Ethanol Appropriate amount The compound of the present invention, citric acid, lactose, dicalcium phosphate, Pluronic F-68 and sodium lauryl sulfate are mixed.

The above mixture is sieved with a No. 60 screen and wet granulated with an alcohol solution containing polyvinylpyrrolidone, carbowax 1500 and 6000. If necessary, alcohol is added to make the powder into a pasty mass. Add corn starch and continue mixing until uniform particles are formed. The mixture was passed through a No. 10 screen, placed in a tray, and placed in an oven at 100 ° C. for 1 hour.
Dry for 2-14 hours. The dried particles are sieved through a No. 16 screen, dry sodium lauryl sulfate and dry magnesium stearate are added, mixed and compressed into the desired shape on a tablet press.

The above core is treated with varnish, and talc is sprayed to prevent moisture absorption. An undercoat layer is coated around the core. Apply varnish a sufficient number of times for internal use. A further subbing layer and a smooth coating are applied to make the tablet completely round and smooth. Color coating is carried out until the desired hue is obtained. After drying, the coated tablets are polished into tablets of uniform gloss.

Formulation Example 3 4-methyl-1- [4- (2,3-dimethylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-1,4-benzodiazepine 5 g polyethylene glycol (Molecular weight: 4000) 0.3 g sodium chloride 0.9 g polyoxyethylene-sorbitan monooleate 0.4 g sodium metabisulfite 0.1 g methyl-paraben 0.18 g propyl-paraben 0.02 g distilled water for injection 10.0 ml The above-mentioned parabens, sodium metabisulfite and sodium chloride are dissolved in about half of the above-mentioned distilled water at 80 ° C. while stirring. The obtained solution is cooled to 40 ° C., and the active ingredient compound of the present invention, and then polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. Next, distilled water for injection is added to the solution to make the final volume, and the solution is sterilized by sterile filtration using an appropriate filter paper to prepare an injection.

<Pharmacological test> Oxytocin receptor binding assay Y. Chan et al. [Endocrinology, 126.2095-2].
101 (1990)], the day before DES (diethylstilbestro
Uterine muscle is excised from the rat to which l) has been injected subcutaneously, and a membrane preparation is prepared using a homogenate. This membrane sample 0.2
mg and [ ³ H] oxytocin at 100,000 dpm (1
0 ^-9 M) and the test compound (10 ^-9 to 10 ^-5 M) at ⁵ mM
1 containing gCl ₂ , 1 mM EDTA and 0.1% BSA
Total amount of 00 mM Tris-HCl buffer (pH = 8.0) 2
Incubated for 1 hour at 25 ° C. in 50 μl. Then, using a glass filter (GF / B),
Filtration was performed to separate the membrane preparation bound to [ ³ H] oxytocin, and the membrane was washed twice with 5 ml of buffer solution. This glass filter was placed in a vial, mixed with aquasol (cocktail for liquid scintillation), the amount of bound [ ³ H] oxytocin was measured with a liquid scintillation counter, and the inhibition rate (%) was calculated by the following equation.

Inhibition rate (%) = 100 − [(C ₁ −B) /
Except test compound; (C ₀ -B)] × 100 C _1; amount of binding ^{of [3} H] oxytocin in the film in a state where a known amount of test compound is ^[3 H] oxytocin coexist C ₀ Amount of [ ³ H] oxytocin bound to the membrane at the time of B: [in the presence of excess oxytocin (5 × 10 ⁻⁶ M)]
^[ H] oxytocin binding amount to the membrane The concentration of the test compound at which the inhibition rate calculated above was 50% was determined, and this was defined as the IC ₅₀ value. The results are shown in Tables 1 to 7 below. The test compounds are as follows.

Test compound No. 1: 3-methyl-1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 2: 5-methyl-1- [4- (2-methylbenzoylamino) benzoyl ] -2,3,4,5-tetrahydro-1H-benzazepine 3: 5-hydroxymethyl-7-chloro-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 4: 4-hydroxy-1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 5: 4-hydroxy-1 -[4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 6: 5-hydroxy-1- [2-methoxy-4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 7: 5-hydroxy-6-methyl-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 8: 4-methyl-5-hydroxy-1- [4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine 9: 5-hydroxy-7-chloro-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 10: 5-hydroxy-7-chloro-1- [2-methyl-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine.

11: 5-hydroxy-7-chloro-1-
[3-methoxy-4- (2-methylbenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine 12: 5-hydroxy-7-chloro-1- {4- [2-
(2-methylphenyl) acetylamino] benzoyl
-2,3,4,5-tetrahydro-1H-benzazepine 13: 5-hydroxy-7-chloro-1- [3-methoxy-4- (2-chlorobenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 14: 5-hydroxy-1- [2-chloro-4- (2,
4-dichlorobenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 15: 5-oxo-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 16: 4 -Oxo-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 17: 5-oxo-1- [2-methoxy-4- (2- Methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 18: 5-oxo-1- [2-methyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-benzazepine 19: 5-hydroxy-6-methyl-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 20: 5-acetyloxy-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine .

21: 4-dimethylaminomethyl-1-
[4- (2-methylbenzoylamino) benzoyl]-
1,2,3,4-tetrahydroquinoline 22: 5-aminomethyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 23: 5- Formylaminomethyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 24: 5-acetyloxymethyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 25: 5-mesyloxymethyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-benzazepine 26: 1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine-5-spiro-2'-oxirane 27: 5-methylaminocarbonyloxy-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 28: 5-carbamoyloxy-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-benzazepine 29: 5-dimethylaminocarbonyloxy-1- [4
-(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 30: 5-carboxymethoxy-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-benzazepine.

31: 5- (4-dimethylaminobutoxy) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 32: 5- (3 -Aminopropoxy) -1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 33: 5- (2-dimethylaminoethoxy) -7-fluoro-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4 , 5-Tetrahydro-1H-benzazepine hydrochloride 34: 5- (3-phthalimidopropoxy) -1- [4
-(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 35: 5-hydroxyimino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 36: 5-acetyloxyimino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 37: 5-methylidene-1- [2-chloro-4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine 38: 5-methylidene-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 39: potassium {1- [ 2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepin-5-yldiimino-O-sulfonate 40: 5- (2-dimethylaminoacetyl Oxy) -1
-[4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine.

41: 5- (2-dimethylaminoacetyloxy) -7-fluoro-1- [2-methoxy-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 42: 5- (2-dimethylaminoacetyloxy) -7
-Chloro-1- [4- (2-chlorobenzoylamino)
-2-methoxybenzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 43: 5- (2-dimethylaminoacetyloxy) -7
-Chloro-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 44: 5- (2-dimethylaminoacetyloxy ) -7
-Chloro-1- [3-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 45: 5- (2-dimethylaminoacetyloxy) -7
-Chloro-1- {2-methoxy-4-[(2-methylphenyl) acetylamino)] benzoyl} -2,3.
4,5-tetrahydro-1H-benzazepine hydrochloride 46: 5- (4-dimethylaminobutyryloxy) -7
-Chloro-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 47: 5- (2-dimethylaminoacetyloxy ) -7
-Fluoro-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 48: 5- (2-dimethylaminoacetyloxy) -7
-Chloro-1- [2-methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 49: 5- (2-aminoacetyloxy) -7-chloro-1- [3-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-benzoazepine hydrochloride 50: 5- (2-aminoacetyloxy) -7-chloro-1- [3-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5- Tetrahydro-1
H-Benzazepine hydrochloride.

51: 5- (2-aminoacetyloxy)
-7-Fluoro-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzoazepine hydrochloride 52: 5- (2-aminoacetyl Oxy) -7-chloro-1- [2-methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine hydrochloride 53: 5-carbamoylmethoxy-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 54: 5-dimethylaminocarbonylmethoxy-1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 55: 5-carbamoylmethylaminocarbonylmethoxy-7-chloro-1- [4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5 -Tetrahydro-
1H-Benzoazepine 56: 5- (4-methyl-1-piperazinylcarbonylmethoxy) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 57: 5-amino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 58: 3-dimethylamino-1- [4 -(3,5-dichlorobenzoylamino) benzoyl] -1,2,3,4
-Tetrahydroquinoline 59: 4-methylamino-1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 60: 4-dimethylamino-1- [3-methoxy-4 −
(2-methylbenzoylamino) benzoyl] -1,
2,3,4-tetrahydroquinoline.

61: 3-dimethylamino-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 62: 5- (N- Methyl-N-ethylamino) -1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 63: 5-dimethylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 64: 5-dimethylamino-1- [2-chloro-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 65: 5-dimethylamino-1- [3-ethoxy-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 66: 5-dimethylamino-1- [3-hydroxy-4
-(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 67: 5-dimethylamino-1- [3-benzyloxy-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 68: 5-dimethylamino-1- [2-ethoxy-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 69: 5-dimethylamino-1- [3-methyl-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 70: 5-dimethylamino-1- [2-fluoro-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine.

71: 5-dimethylamino-1- [3-fluoro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 72: 5-dimethylamino- 1- [3-methoxy-4-
(2,3-dimethylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzoazepine 73: 5-dimethylamino-1- [4- (2-methylanilinocarbonyl) benzoyl] -2,3,4,5-tetrahydro-1H-benzo Azepine 74: 5-dimethylamino-1- [3-hydroxy-4
-(2-chlorobenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 75: 3-hydroxy-4-dimethylamino-1- [4
-(2-methylbenzoylamino) benzoyl] -1,
2,3,4-tetrahydroquinoline 76: 4-methyl-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 77: 5-methylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 78: 5-methylamino-1- [2-methyl-4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 79: 5-methylamino-1- [2-chloro-4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 80: 5-propylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine. 81: 5-ethylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 82: 5-allylamino-1- [2-chloro-4 -(2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 83: 5-acetylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 84: 5- (N-acetyl-N-methylamino) -1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 85: 5-cyclopropylamino-1- [2-chloro-
4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 86: 5- (2-dimethylaminoethylamino) -1-
[2-Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 87: 5- (3-dimethyl-2-hydroxypropylamino) -1- [ 4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 88: 5- (2,3-dihydroxypropylamino)-
1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 89: 5- [N- (3-hydroxypropyl) -N-methylamino] -1 -[4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 90: 5-benzoylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine.

91: 5- (N-cyanomethyl-N-methylamino) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 92: 5- (N-carbamoylmethyl-N-methyl) amino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzoazepine 93 : 5- [N- (3- [1-tetrahydropyranyloxy] propyl) -N-methyl] amino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 94: 5- [N- (3-acetyloxypropyl) -N
-Methyl] amino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 95: 5- (1-benzyl-4-piperidinyl) amino-1 -[4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 96: 3- (4-methyl-1-piperazinyl) -1-
[4- (2,3-dimethylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 97: 3- (1-pyrrolidinyl) -1- [4- (2,3
-Dimethylbenzoylamino) benzoyl] -1,2,2.
3,4-tetrahydroquinoline 98: 5-hydroxy-5-hydroxymethyl-1-
[2-Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1-benzazepine 99: 5-hydroxy-5-hydroxymethyl-1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 100: 5-hydroxymethyl-5-N-methylamino-
1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine.

101: 5-hydroxy-5-N-methylamino) methyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 102: 5-hydroxy-5-methyl-1- [4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-Tetrahydro-1H-benzazepine 103: 5- (N-ethoxycarbonylmethyl-N-methylamino) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro- 1
H-Benzoazepine 104: 1- [4- (2-methylbenzoylamino) benzoyl-1,2,3,5-tetrahydro-4,1-benzoxazepine 105: 1- [4- (2-methylbenzoyl) Amino) benzoyl] -1,2,3,4-tetrahydro-5,1-benzoxazepine 106: 4-methyl-1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3 4-tetrahydroquinoxaline 107: 4-methyl-1- [4- (3,5-dichlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-1,4-benzodiazepine 108: 5-methyl- 1- (4-benzoylaminobenzoyl) -2,3,4,5-tetrahydro-1H-1,5
-Benzodiazepine 109: 4-isopropyl-1- [4- (2,3-dimethylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-1,4-benzodiazepine 110: 1- [4- (2-methylbenzoylamino) benzoyl] -1,2-dihydroquinoline.

111: 5- [2- (4-morpholino) acetyloxy] -7-chloro-1- [2-methoxy-4-
(2-methylbenzoylamino) benzoyl-2,3,
4,5-tetrahydro-1H-benzazepine hydrochloride 112: 5- (2-isopropylaminoacetyloxy)
-7-chloro-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzoazepine hydrochloride 113: 5- (1,5- Diaminopentylcarbonyloxy) -7-chloro-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl-2,3,4,5-
Tetrahydro-1H-benzazepine hydrochloride 114: 5- (3-aminopropionyloxy) -7-chloro-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4 5-tetrahydro-1H-benzazepine hydrochloride 115: 5- (4-dimethylaminobutyryloxy) -7
-Chloro-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 116: 5- (1,5-diaminopentyl) Carbonyloxy) -7-chloro-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine hydrochloride 117: 5- (3-aminopropionyloxy) -7-fluoro-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4 , 5-Tetrahydro-1H-benzazepine hydrochloride 118: 5-formyloxy-7-chloro-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 119: 5-dimethylaminocarbonylmethyl-7-chloro-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro- 1H-Benzoazepine 120: 1- [4- (3-methylphenylsulfonylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzazepine.

121: 1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 122: 1- [4- (4-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 123: 1- [4- (2,3-dimethylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 124: 1- [4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 125: 1- [4- (2-bromobenzoylamino) benzoyl ] -2,3,4,5-tetrahydro-1H-benzazepine 126: 1- [4- (2-methoxybenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 127: 1 -(4-cyclohexylcarbonylaminobenzoyl) -2,3,4,5-tetrahydro-1H-benzazepine 128: 1- [4- (2-carbamoylmethoxybenzoylamino) benzoyl] -2,3,4,5- Tetrahydro-1H-benzazepine 129: 1- {4- [2- (6-isopropylaminohexyloxy) benzoylamino] benzoyl}- ,
3,4,5-tetrahydro-1H-benzazepine 130: 1- [4- (2- (N-phenyl-N-ethynylamino) acetylamino) benzoyl] -2,3,4.
5-tetrahydro-1H-benzazepine.

131: 1- [4- (2- (N-phenyl-
N-methylamino) acetylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 132: 1-[(2- (4-phenylamino) acetylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 133: 1-[｛4- (2- [N-phenyl-N- (2-
Acetyloxy) ethoxy] amino) acetylamino
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine 134: 1-{[4- (2- (2-acetylaminophenoxy) acetylamino)] benzoyl} -2,3,4
5-tetrahydro-1H-benzazepine 135: 1- [4- (3-fluorobenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 136: 1- [4-tricyclo (3,3,1 , 1) Decanylcarbonylaminobenzoyl] -1,2,3,4-
Tetrahydroquinoline 137: 1- (4-benzylcarbonylaminobenzoyl) -1,2,3,4-tetrahydroquinoline 138: 1- [4- (2-furoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline 139: 1- [4- (3-thenoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline 140: 1- [4- (3-ethoxybenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline.

141: 7-chloro-1- [4- (3-hydroxybenzoylamino) benzoyl] -2,3,4
5-Tetrahydro-1H-benzazepine 142: 7-chloro-1- [4- (3-acetyloxybenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 143: 7-chloro- 1- [4- (2-carbamoylmethoxybenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 144: 7-chloro-1- {3- [2- (2-dimethylaminoethoxy) benzoylamino] benzoyl} -2,
3,4,5-tetrahydro-1H-benzazepine hydrochloride 145: 7-chloro-1- {4- [2- (4-isopropylaminobutoxy) benzoylamino] benzoyl}-
2,3,4,5-tetrahydro-1H-benzoazepine 146: 1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3,4,5,6-hexahydrobenzoazosin 147: 1- [4- (2-methoxybenzoylamino) benzoyl] -1,2,3,4,5,6-hexahydrobenzoazosin 148: 6-methyl-1- [4- (3,5-dichlorobenzoyl) Amino) benzoyl] -1,2,3,4-tetrahydroquinoline 149: 1- [4- (3-methylbenzoylamino) benzoyl] perhydroquinoline 150: 1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline.

151: 1- [4- (4-methoxycarbonylbenzoylamino) benzoyl] -1,2,3,4-
Tetrahydroquinoline 152: 1- [4- (2-nitrobenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 153: 1- (4-isobutyrylaminobenzoyl)-
1,2,3,4-tetrahydroquinoline 154: 1- [4- (2,3-dimethylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 155: 4-methyl-1- [4-cyclohexylcarbonylaminobenzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 156: 3-methyl-1- [4- (2-methyl Benzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 157: 2-methyl-1- (4-benzoylaminobenzoyl) -1,2,3,4-tetrahydroquinoline 158: 1- {4- [ 4- (6- (1-piperidyl) hexyloxy) benzoylamino] benzoyl} -2,
3,4,5-tetrahydro-1H-benzazepine 159: 1- [4- (2-Chloro-4-aminobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 160: 3 -Dimethylaminocarbonyl-1- [4-
(3,5-dichlorobenzoylamino) benzoyl]-
1,2,3,4-tetrahydroquinoline.

161: 1- {4- [2- (4-methoxyanilino) acetylamino] benzoyl} -2,3,4
5-Tetrahydro-1H-benzazepine 162: 1- {4- [2- (2- (4-morpholino) ethoxy) benzoylamino] benzoyl} -2,3,4.
5-tetrahydro-1H-benzazepine 163: 1- {4- [2- (4-hydroxybutoxy) benzoylamino] benzoyl} -2,3,4,5-tetrahydro-1H-benzazepine 164: 1- {4 -(2-diethylaminocarbonylmethoxybenzoylamino) benzoyl} -2,3,4,5
-Tetrahydro-1H-benzazepine 165: 1- {4- (2- [N- (1- (2-propyl)), N- (phenyl) amino] acetylamino) benzoyl} -2,3,4,5 -Tetrahydro-1H-benzazepine 166: 4-isopropyl-1- {4- (2,3-dimethylbenzoylamino) benzoyl} -2,3,4,5-
Tetrahydro-1H-1,4-benzodiazepine 167: 1- {4- [4- (2-diethylaminoacetyl-1-piperidinyl) carbonylamino] benzoyl}
-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 168: 5-methoxy-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benazepine 169: 5-ethoxycarbonylmethoxy-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 170: 5-hydroxymethyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine.

171: 1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine-5-spiro-2'-oxirane 172: 5- [N- Methyl, N- (2-hydroxy-3-
Diethylaminopropyl)] amino-1- [4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-Tetrahydro-1H-benzazepine 173: 5- (N-methyl, Nn-propyl) amino-
1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 174: 5- (4-morpholinocarbonylmethoxy) -1
-[4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 175: 5- (4-thiomorpholinocarbonylmethoxy)
-1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 176: 5- (anilinocarbonylamino) -1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 177: 5-isobutylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 178: 5-formylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 179: 5- (1-oxothiomorpholinocarbonylmethoxy) -1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 180: 5-methylaminocarbonylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine.

181: 5- (1-pyrrole) -1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 182: 5-[(2S) -2-carbamoyl- (1-pyrrolidinyl)] carbonylmethoxy-1- [4- (2-methylbenzoylamino) benzoyl] -2 , 3,4,5
-Tetrahydro-1H-benzazepine 183: 5-carbamoylmethylaminocarbonylmethoxy-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 184: 5- [(1,1-Dioxothiomorpholino) carbonylmethoxy] -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 185: 5-[( 4-acetyl-1-piperazyl) carbonylmethoxy] -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 186: 7-chloro-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 187: 5-ethoxycarbonylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 188: 5- (2-methylamino) acetylamino-1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 189: 5- [N-methyl, N- (2-hydroxyethyl) aminocarbonylmethoxy] -1- [4- (2-methylbenzoylamino) benzoyl] −2,3,4,5
-Tetrahydro-1H-benzazepine 190: 5-dimethylamino-1- [4- (2-methylbenzoyloxy) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine.

191: 2- [N-methyl-N- ｛1- [4
-(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine-5
-Ill @ amino] acetic acid / potassium salt 192: 5- (2- [N-methyl, N- (1-imidazole)] acetylamino) -1- [4- (2-methylaminobenzoylamino) benzoyl] -2 , 3,4,5-
Tetrahydro-1H-benzazepine 193: 5-dimethylamino-1- [4- (2-dimethylaminobenzoylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine 194: 5- (2-aminoacetylamino) -1- [4-
(2-methylaminobenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 195: 5- [2- (1-imidazole) acetylamino] -1- [4- (2-methylaminobenzoylamino) benzoyl] -2,3. 4,5-tetrahydro-1
H-Benzoazepine 196: 8-chloro-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 197: 8-chloro-5-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 198: 5- (2-tert-butoxycarbonylamino) acetylamino) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5- Tetrahydro-1H-benzazepine 199: 6-chloro-5-hydroxy-1- [4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine 200: 6-chloro-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine.

201: 7-chloro-5-cyclopropylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 202: 9-chloro- 5-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 203: 9-chloro-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 204: 5-dimethylamino-1- [4- (2-methylbenzylcarbonylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine 205: 6-methylamino-1- [4- (2-methylbenzoylamino) benzoyl] -1,2,3,4,5,6
-Hexahydrobenzazosin 206: 7-chloro-5-methylamino-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzoazepine 207: 7-chloro-5-dimethylamino-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 208: 7-chloro- 5-cyclopropylamino-1-
[3-methoxy-4- (2-methylbenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine 209: 7-methoxy-5-oxo-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 210: 7-methyl-5-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine.

211: 7-methyl-5-cyclopropylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 212: 7-methyl- 5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 213: 7-methoxy-5-oxo-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 214: 7-methoxy-5-methylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4 5-tetrahydro-1H-benzazepine 215: 7-bromo-5-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 216: 7-chloro-5-methylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 217: 7-chloro-5-cyclopropylamino-1-
[2-Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 218: 7-chloro-5-dimethylamino-1- [2-chloro-4 -(2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 219: 7-methyl-5- (N-methyl, N-ethyl) amino-1- [4- ( 2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 220: 7-bromo-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine.

221: 7-methoxy-5-methylamino-
1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 222: 7-methoxy-5-methylamino-1- [3-methoxy-4- ( 2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 223: 7-methoxy-5-dimethylamino-1- [2-
Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 224: 7-methyl-5-methylamino-1- [2-chloro-4- (2 -Methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 225: 7-methoxy-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 226: 7-methyl-5-cyclopropylamino-1-
[2-Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 227: 7-chloro-5-allylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 228: 7-chloro-5-dimethylamino-1- [2-methyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4 , 5-Tetrahydro-1H-benzazepine 229: 6-methylamino-1- [2-chloro-4- (2
-Methylbenzoylamino) benzoyl] -1,2,2
3,4,5,6-hexahydrobenzazocine 230: 7-methoxy-5-dimethylamino-1- [3-
Methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine.

231: 7-methoxy-5-cyclopropylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 232: 7-chloro-5-ethylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 233: 7-methoxy-5-cyclopropyl-1- [3-
Methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 234: 7-dimethylamino-5-oxo-1- [2-chloro-4- (2 -Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 235: 8-chloro-6-methylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl ]
-1,2,3,4,5,6-hexahydrobenzazocine 236: 7-methoxy-5-cyclopropylamino-1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 237: 7-methoxy-5-hydroxy-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 238: 6-chloro-4-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -1,2,2
3,4-tetrahydroquinoline 239: 7-dimethylamino-5-methylamino-1-
[2-Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 240: 7-methyl-5-dimethylamino-1- [2-chloro-4 -(2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine.

241: 7-dimethylamino-5-hydroxy-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 242: 6-chloro-4-methylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline 243: 7-chloro-5-methylamino-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro -1H-benzoazepine 244: 7-chloro-5-dimethylamino-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzoazepine 245 : (+) 5-dimethylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine hydrochloride 246: (-) 5-dimethylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine hydrochloride 247: 7-chloro-5-cyclopropylamino-1-
[2-Methyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 248: 7-methyl-5-methylamino-1- [2-chloro-4 -(2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 249: 8-methoxy-6-methylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -1,2,3 , 4,5,6-hexahydrobenzazocine 250: 7-methoxy-5-methylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -1,
2,3,4-tetrahydroquinoline.

251: 6-methoxy-4-methylamino-
1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 252: 7-fluoro-5-cyclopropylamino-1-
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 253: 7-fluoro-5-cyclopropylamino-1-
[2-Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 254: 7-fluoro-5-cyclopropyl-1- [3-
Methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 255: 6-methoxy-4-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -1,
2,3,4-tetrahydroquinoline 256: 6-methoxy-4-dimethylamino-1- [2-
Chloro-4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 257: 7-methyl-5-methylamino-1- [3-methoxy-4- (2-methylbenzoylamino ) Benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 258: 7-methyl-5-dimethylamino-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2, 3,4,5-tetrahydro-1H-benzazepine 259: 6-chloro-4-methylamino-1- [2-methyl-4- (2-methylbenzoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline 260: 7-chloro-5-dimethylamino-1- [2-methyl-4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydro Quinoline.

261: 7-fluoro-5-methylamino-
1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 262: 7-fluoro-5-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 263: 7-fluoro-5-dimethylamino-1- [2-
Chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 264: 7-chloro-5-allylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-Tetrahydro-1H-benzazepine 265: 7-chloro-5- (N-methyl, N-allyl) amino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4, 5-tetrahydro-1H-benzazepine 266: 7-fluoro-5-dimethylamino-1- [3-
Methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 267: 7-methoxy-5-methylamino-1- [2-methyl-4- (2 -Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 268: 7-methoxy-5-dimethylamino-1- [2-
Methyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 269: 6-methyl-4-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -1,2,2
3,4-tetrahydroquinoline 270: 6-chloro-4-methylamino-3-methyl-1
-[4- (2-methylbenzoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline.

271: 4-methylamino-3-methyl-1
-[4- (2-methylbenzoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline 272: 6-chloro-4-methylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-1,2,3,4-tetrahydroquinoline 273: 6-chloro-4-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -1,
2,3,4-tetrahydroquinoline 274: 6-chloro-4-dimethylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 275: 6-methyl-4-dimethylamino-1- [4-
(2-methylbenzoylamino) benzoyl] -1,
2,3,4-tetrahydroquinoline 276: 6-methyl-4-dimethylamino-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 277: 6-chloro-4-dimethylamino-3-methyl-
1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 278: 4-dimethylamino-3-methyl-1- [2-chloro-4- ( 2-methylbenzoylamino) benzoyl] -1,2,3,4-tetrahydroquinoline 279: 8-chloro-6-methylamino-1- [4- (2
-Methylbenzoylamino) benzoyl] -1,2,2
3,4,5,6-hexahydrobenzazocine 280: 7-chloro-5-allylamino-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5- Tetrahydro-1H-benzazepine.

281: 7-chloro-5- (N-methyl, N
-Ethyl) amino-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 282: 7-chloro-5- (N-methyl, N-allyl) amino-1- [3-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4 , 5-Tetrahydro-1H-benzazepine 283: 7-fluoro-5-hydroxy-1- [4- (2
-Methylbenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine 284: 7-fluoro-5-hydroxy-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 285: 7-fluoro-5-hydroxy-1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4 5-tetrahydro-1H-benzazepine 286: 5-dimethylamino-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 287: 5-chloro- 1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 288: 7-methoxy-5-methylidene-1- [2-chloro-4- (2 -Methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 289: 7-chloro-4-methyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-1,4-benzodiazepine 290: 4-methyl-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-1,4-benzodiazepine.

291: 7-methoxy-5-hydroxymethyl-5-hydroxy-1- [2-chloro-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 292: 7-methoxy-5-methylamino-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzo Azepine 293: 7-methoxy-5-hydroxy-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 294: 7-fluoro- 5- [2- (4-methyl-1-piperazinyl) ethoxy] -1- [2-methoxy-4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 295: 7-chloro-1- {2-methoxy-4- [2-
(4- [4-Methyl-1-piperazinyl] butoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 296: 7-chloro-5- (2- (isopropylamino)
Ethoxy) -1- [2-methyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 297: 7-chloro-5- (4- Methyl-1-piperazinyl) carbonylmethyl-1- [2-chloro-4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine hydrochloride 298: 7-chloro-1- {3-methoxy-4- [2-
(2-Dimethylaminoethoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 299: 7-chloro-5- (4-methyl-1-piperidinyl) carbonylmethyl-1- [ 4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 300: 7-chloro-5- (2-dimethylaminoethyl)
-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-benzoazepine hydrochloride.

301: 7-chloro-4-hydroxy-1-
[2-methoxy-4- (2-methylbenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine 302: 7-chloro-1- [2-chloro-4- (2-acetyloxybenzoylamino) benzoyl] -2,3.
4,5-tetrahydro-1H-benzazepine 303: 7-chloro-1- [2-chloro-4- (2-hydroxybenzoylamino) benzoyl] -2,3,4.
5-tetrahydro-1H-benzazepine 304: 7-chloro-1- [2-methyl-4- (2-hydroxybenzoylamino) benzoyl] -2,3,4.
5-tetrahydro-1H-benzazepine 305: 7-fluoro-5-[(4-dimethylamino-1
-Piperidino) carbonylmethyl] -1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 306: 7-fluoro-5- (1-piperidinocarbonylmethyl) -1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl ] -2,3,4,5-tetrahydro-1H-benzazepine 307: 7-chloro-5-[(1-methyl-4-piperidinyl) aminocarbonylmethoxy] -1- [2-methyl-4- (2 -Methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine hydrochloride 308: 7-chloro-5- (2-acetylaminoethyl)
-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 309: 7-chloro-5-dimethylaminocarbonylmethyl-1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 310: 7- Chloro-5-carbamoylmethyl-1- [4
-(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine.

311: 7-chloro-5-[(4-methyl-
1-piperazinyl) carbonylmethoxy] -1- [4-
(2-methylbenzoylamino) benzoyl] -2,
3,4,5-tetrahydro-1H-benzazepine 312: 7-fluoro-5-[(4-acetylamino-1
-Piperidino) carbonylmethyl] -1- [4- (2-
Methylbenzoylamino) benzoyl] -2,3,4
5-tetrahydro-1H-benzazepine 313: 7-chloro-5-[(4-acetylamino-1-
Piperidino) carbonylmethyl] -1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 314: 5-[(4-acetylamino-1-piperidino)
Carbonylmethyl] -7-fluoro-1- [2-methoxy-4- (2-bromomethylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 315: 7-chloro-1- [2-Chloro-4- (2-carbamoylmethoxybenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 316: 7-chloro-1- {2-chloro-4- [2- (2
-Dimethylaminoethoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 317: 7-chloro-1- {2-chloro-4- [2- (4
-Dimethylaminobutoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 318: 7-chloro-1- {2-chloro-4- [2- (4
-Isopropylaminobutoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 319: 7-chloro-1- {2-methyl-4- (2-carbamoylmethoxy) benzoylamino] benzoyl ｝-
2,3,4,5-tetrahydro-1H-benzazepine 320: 7-chloro-5- (2-hydroxyethyl) -1
-[4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine.

321: 7-chloro-5- (2-hydroxyethyl) -1- [4- (2-chlorobenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine 322: 7-chloro-5- (2-hydroxyethoxy)-
1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 323: 7-chloro-5- (2-hydroxyethoxy)-
1- [4- (2-Chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 324: 7-chloro-5- (2-dimethylaminoethyl)
-1- [4- (2-Chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 325: 7-chloro-5- (2-chloroethyl) -1-
[4- (2-chlorobenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 326: 7-chloro-5- (2-dimethylaminoethyl)
-1- [4- (2-Methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 327: 7-chloro-5- (2-isopropylaminoethyl) -1- [4 -(2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 328: 7-chloro-5- (2-isopropylaminoethyl) -1- [4- (2-methyl Benzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 329: 7-chloro-5- (2-tert-butylaminoethyl) -1- [4- (2-chlorobenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine 330: 7-chloro-5- (2-tert-butylaminoethyl) -1- [4- (2-methylbenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine.

331: 7-chloro-5- (2-isopropylaminoethoxy) -1- [4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 332: 7-chloro-5- (2-isopropylaminoethoxy) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 333: 7-chloro-5 -(2-tert-butylaminoethoxy) -1- [4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 334: 7-chloro-4-methylamino-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzoazepine 335: 7-chloro-4-dimethylamino-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 336: 7-chloro-5- (2-dimethylaminoethyl)
-1- [2-methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 337: 7-chloro-5- (2-diethylaminoethyl)
-1- [2-methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1
H-Benzoazepine 338: 7-chloro-5- (2-isopropylaminoethyl) -1- [2-methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benazepine 339: 7-chloro-5- (2-tert-butylaminoethyl) -1- [2-methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro- 1H-Benzoazepine 340: 7-chloro-5- (2-dimethylaminoethoxy) -1- [3-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benzazepine.

341: 7-chloro-5- (2-diethylaminoethoxy) -1- [3-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-
Tetrahydro-1H-benzazepine 342: 7-chloro-5- (2-isopropylaminoethoxy) -1- [3-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro -1H-Benzoazepine 343: 7-chloro-5- (2-diethylaminoethoxy) -1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benazepine 344: 7-chloro-5- (2-isopropylaminoethoxy) -1- [3-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H- Benzoazepine 345: 7-chloro-5- (2-tert-butylethoxy) -1- [3-methoxy-4- (2-methylbenzoylamino) benzo Le] -2,3,4,5-tetrahydro -1H- benzoazepine 346: 7-chloro-5- (2-diethylaminoethyl)
-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 347: 7-chloro-5- (2-isopropylaminoethyl) -1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benazepine 348: 7-chloro-5- (2-tert-butylaminoethyl) -1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro- 1H-Benzoazepine 349: 7-chloro-5- (2-diethylaminoethyl)
-1- [2-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 350: 7-chloro-5- (2-isopropylaminoethyl) -1- [2-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benzazepine.

351: 7-chloro-5- (2-tert-
Butylaminoethyl) -1- [2-methoxy-4- (2
-Chlorobenzoylamino) benzoyl] -2,3,
4,5-Tetrahydro-1H-benzazepine 352: 7-chloro-1- [2-methoxy-4- (3-hydroxybenzoylamino) benzoyl] -2,3.
4,5-tetrahydro-1H-benzazepine 353: 7-chloro-1- [3-methoxy-4- (2-hydroxybenzoylamino) benzoyl] -2,3.
4,5-tetrahydro-1H-benzazepine 354: 7-chloro-1- [3-methoxy-4- (2-carbamoylmethoxybenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine 355: 7-chloro-1- {3-methoxy-4- [2-
(2-Dimethylaminoethoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 356: 7-chloro-1- {3-methoxy-4- [2-
(2-Isopropylaminoethoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1
H-Benzoazepine 357: 7-chloro-1- {3-methoxy-4- [2-
(4-Dimethylaminobutoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1H-benzazepine 358: 7-chloro-1- {3-methoxy-4- [2-
(4-Isopropylaminobutoxy) benzoylamino] benzoyl {-2,3,4,5-tetrahydro-1
H-Benzoazepine 359: 7-chloro-4-hydroxy-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl]
-2,3,4,5-tetrahydro-1H-benzazepine 360: 7-chloro-5- (2-aminoethyl) -1-
[2-methoxy-4- (2-methylbenzoylamino)
Benzoyl] -2,3,4,5-tetrahydro-1H-
Benzoazepine hydrochloride.

361: 7-chloro-4-hydroxy-1-
[2-Methyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 362: 7-chloro-1- [2-methyl-4- (2-acetyl Oxybenzoylamino) benzoyl] -2,3
4,5-tetrahydro-1H-benzazepine 363: 7-chloro-5-carbamoylmethoxy-1-
[2-Methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 364: 7-fluoro-5- (2-diethylaminoethyl) -1- [2 -Methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 365: 7-fluoro-5- (2-isopropylaminoethyl) -1- [2- Methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 366: 7-fluoro-5- (2-tert-butylaminoethyl) -1- [2 -Methyl-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H-benzazepine 367: 7-chloro-5- (2-ethylamino Butoxy)
-1- [2-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-
1H-Benzoazepine 368: 7-chloro-5- (2-acetylaminoethoxy) -1- [2-methoxy-4- (2-chlorobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H -Benazepine 369: 7-chloro-5- (2-isopropylaminoethoxy) -1- [2-methoxy-4- (2-bromobenzoylamino) benzoyl] -2,3,4,5-tetrahydro-1H- Benzoazepine 370: 7-chloro-5-methoxy-1- [2-methoxy-4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine.

371: 7-chloro-5- {N-methyl, N
-[2- (2-pyridyl) ethyl] aminocarbonylmethoxy-1- [2-trifluoromethyl-4- (2-methylbenzoylamino) benzoyl] -2,3,4,5
-Tetrahydro-1H-benzazepine 372: 7-chloro-5- [2- (N-ethyl, N-butylamino) ethoxy] -1- [2-methoxy-4- (2
-Chlorobenzoylamino) benzoyl] -2,3,
4,5-tetrahydro-1H-benzazepine

[0145]

[Table 1]

[0146]

[Table 2]

[0147]

[Table 3]

[0148]

[Table 4]

[0149]

[Table 5]

[0150]

[Table 6]

[0151]

[Table 7]

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/495 A61K 31/495 31/55 31/55 // C07D 215/08 C07D 215/08 223/16 223/16 A 225 / 06 225/06 241/42 241/42 243/14 243/14 265/36 265/36 267/14 267/14 403/12 223 403/12 223 405 405 405/12 409/12 409/12 417 / 12 417/12 491/107 491/107 (72) Inventor Kenji Nakaya 48, Kamibetsugu-Kita, Kawauchi-cho, Tokushima City, Tokushima Prefecture (72) Inventor Riki Tanaka Inamoto 21-1 (1) 72) Inventor Kazuyoshi Kitano 463-10 Kagasuno, Kawauchi-machi, Tokushima City, Tokushima Prefecture (72) Keizo Suga 463-10 Kasuno, Kawauchi-machi, Tokushima City, Tokushima Prefecture (72) Michiaki Tominaga Takaiso, Kamiita-cho, Itano-gun, Tokushima Prefecture 310-6 (72) Inventor Yoichi Yabuuchi 900-25 Omatsu, Kawauchi-cho, Tokushima City, Tokushima Prefecture (56) References JP-A-4-154765 (JP, A) JP-A-63-126893 (JP, A) JP-A-60-54326 (JP, A) JP-A-58-222060 (JP, A) JP-A-56-150050 (JP, A) (58) Int.Cl. ⁶ , DB name) C07D 215/08 C07D 223/16 C07D 225/06 C07D 241/42 C07D 243/14 C07D 265/36 C07D 267/14 C07D 403/12 C07D 405/12 C07D 409/12 C07D 417/12 C07D 491/107 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A compound of the general formula [In the formula, R ¹ represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group or a lower alkoxy group which may have a lower alkyl group as a substituent. R ² is a hydrogen atom,
Halogen atom, lower alkoxy group, phenyl lower alkoxy group, hydroxyl group, lower alkyl group, amino group which may have a lower alkyl group, carbamoyl-substituted lower alkoxy group, amino-substituted lower alkoxy which may have a lower alkyl group as a substituent A benzoyloxy group which may have a halogen atom as a substituent on a group or a phenyl ring. R ³ is a group —NR ⁴ R ⁵ or a group —CONR
¹¹ R ¹² is shown. R ⁴ represents a hydrogen atom, a benzoyl group or a lower alkyl group which may have a halogen atom as a substituent on the phenyl ring. R ⁵ is a group [R ¹⁶ is a halogen atom, a lower alkyl group which may have a halogen atom or a hydroxyl group as a substituent, a hydroxyl group, a lower alkoxy group, a lower alkanoyloxy group, a lower alkylthio group, a lower alkanoyl group, a carboxy group, a lower alkoxycarbonyl group, Amino group, phenyl group, cycloalkyl group, lower alkanoyloxy-substituted lower alkoxy group, carboxy-substituted lower alkoxy group, halogen-substituted lower alkoxy group, carbamoyl substitution which may have a cyano group, nitro group, lower alkyl group or lower alkanoyl group A lower alkoxy group, a hydroxyl-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a phthalimide-substituted lower alkoxy group, an aminocarbonyl lower alkoxy group having a lower alkyl group as a substituent or a group -OA NR ⁶ R ⁷ (A is a lower alkylene group, R ⁶ and R ⁷ are the same or different and each represents a hydrogen atom, a lower alkyl group which may have a hydroxyl group as a substituent, a lower alkanoyl group or a benzoyl group .R ⁶ and R ⁷
May form a 5- or 6-membered saturated heterocyclic ring with or without a nitrogen atom or an oxygen atom together with the nitrogen atom to be bonded. The heterocyclic ring may be substituted with a group selected from the group consisting of a piperidinyl group and a lower alkyl group). m represents an integer of 0 to 3], phenyl lower alkoxycarbonyl group, lower alkanoyl group, phenyl lower alkanoyl group, cycloalkyl lower alkanoyl group, cycloalkylcarbonyl group, tricyclo [3.3.1.1] decanyl A carbonyl group, a naphthylcarbonyl group, a pyridylcarbonyl group, a furoyl group, a thenoyl group, a lower alkyl group as a substituent on a phenyl ring, a lower alkoxy group and an amino group which may have a lower alkanoyl group as a substituent. Phenoxy lower alkanoyl group, phthalimido-substituted lower alkanoyl group, lower alkoxycarbonyl lower alkanoyl group, carboxy lower alkanoyl group, naphthyloxy lower alkanoyl group, halogen-substituted lower alkanoyl group, Chemical formula 3] (R ⁸ represents a hydrogen atom, a lower alkyl group, a phenyl lower alkoxycarbonyl group, a carbamoyl lower alkyl group, an amino lower alkanoyl group or a lower alkanoyl group which may have a lower alkyl group as a substituent), substituted on the phenyl ring Anilinocarbonyl group which may have a lower alkyl group as a group, phenoxycarbonyl group, phenylsulfonyl group which may have a group selected from the group consisting of a halogen atom and a lower alkyl group as a substituent on a phenyl ring, quinolyl Sulfonyl group or group -C
OB- (CO) _n -NR ⁹ R ¹⁰ (B is a lower alkylene group, n is an integer of 0 or 1. R ⁹ and R ¹⁰ may be the same or different, and may have a hydrogen atom or a hydroxyl group as a substituent. Lower alkyl group, cycloalkyl group, phenyl lower alkyl group, lower alkanoyl group, lower alkenyl group, phenoxy lower alkyl group, amino lower alkyl group which may have a lower alkanoyl group as a substituent on the phenyl ring, lower alkyl group, A phenyl group having from 1 to 3 groups selected from the group consisting of lower alkoxy and halogen atoms, a phthalimide-substituted lower alkyl group,
It represents an amino lower alkyl group which may have a lower alkanoyl group as a substituent, a lower alkynyl group or an amino lower alkyl group which may have a lower alkyl group as a substituent. Further, R ⁹ and R ¹⁰ may form a 5- to 6-membered saturated heterocyclic ring together with or without a nitrogen atom to be bonded via a nitrogen atom or an oxygen atom. The heterocyclic ring may be substituted with a group selected from the group consisting of a lower alkyl group, a lower alkoxycarbonyl group and a piperidinyl group). R ¹¹ represents a hydrogen atom or a lower alkyl group. R ¹² represents a cycloalkyl group or a phenyl group which may have 1 to 3 groups selected from the group consisting of a lower alkoxy group, a lower alkyl group and a halogen atom on a phenyl ring. W is a group-(CH ₂ ) _p- (p is 3-
5 integer) or a group _{-CH = CH- (CH 2) q} - (q represents an integer of 1 to 3). The group — (CH ₂ ) _p — and the group —
CH = CH- (CH ₂ ) _q-wherein the carbon atom is an oxygen atom,
Sulfur atom, sulfinyl group, sulfonyl group or group -NR
^13- (R ¹³ represents a hydrogen atom, a cycloalkyl group or a lower alkyl group). Further, the group-(C
H ₂ ) _p — or a group —CH ＝ CH— (CH ₂ ) _q — in which, as a substituent, a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a hydroxyl group, an oxo group, or a substituent A lower alkanoyloxy group which may have a halogen atom, an amino lower alkyl group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, a lower alkanoyloxy-substituted lower alkyl group, a lower alkylsulfonyl An oxy lower alkyl group, an azide lower alkyl group, a group -OCH _2- , an aminocarbonyloxy group which may have a lower alkyl group as a substituent, a lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group,
A carboxy-substituted lower alkoxy group, an aminocarbonyl lower alkoxy group which may have a lower alkyl group as a substituent, an amino lower alkoxy group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent, Phthalimide-substituted lower alkoxy group, hydroxyimino group, lower alkanoyloxyimino group, lower alkylidene group, halogen atom, azide group,
Sulfoxyimino group, group (R ¹⁷ represents a hydrogen atom or a lower alkyl group), a hydrazino group, a pyrrolyl group, an amino lower alkanoyloxy group which may have a lower alkyl group as a substituent, a group-
OA-CONR ¹⁸ R ¹⁹ (A is the same as above. R ¹⁸ and R
¹⁹ is the same or different and is a hydrogen atom, a lower alkyl group,
A carbamoyl-substituted lower alkyl group, a hydroxyl-substituted lower alkyl group or a pyridyl lower alkyl group; Also this R
¹⁸ and R ¹⁹ are a nitrogen atom together with the nitrogen atom to which they are attached,
5 with or without oxygen or sulfur atoms
A 6- to 6-membered saturated heterocyclic ring may be formed. An oxo group, a lower alkyl group, a lower alkanoyl group or a carbamoyl group may be substituted on the heterocyclic ring) and a group-(C
O) _n NR ¹⁴ R ¹⁵ (n is the same as above. R ¹⁴ and R ¹⁵ are the same or different and are a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkanoyl group, cycloalkyl group, oxiranyl-substituted lower alkyl group, substituted A lower alkyl group having one or two groups selected from the group consisting of a lower alkoxy group, a hydroxyl group and an amino group which may have a lower alkyl group as a substituent, a phenyl lower alkyl group, a pyridyl lower alkyl group, a lower alkyl group A sulfonyl group, a benzoyl group, a lower alkoxycarbonyl group, an anilinocarbonyl group, an aminocarbonyl group which may have a lower alkyl group as a substituent, a cyano-substituted lower alkyl group,
Lower alkoxycarbonyl-substituted lower alkyl group, carbamoyl-substituted lower alkyl group, carboxy-substituted lower alkyl group, tetrahydropyranyloxy-substituted lower alkyl group, lower alkanoyloxy-substituted lower alkyl group, phenyl lower alkyl group as a substituent on the piperidine ring May be a piperidinyl group, a halogen-substituted lower alkanoyl group, an imidazolyl-substituted lower alkanoyl group, an amino-lower alkanoyl group which may have a group selected from the group consisting of a lower alkyl group and a lower alkoxycarbonyl group as a substituent, and a lower group as a substituent. It represents an aminocarbonyl lower alkyl group or a phenyl lower alkoxycarbonyl group which may have an alkyl group. R ¹⁴ and R ¹⁵ may form a 5- to 6-membered saturated heterocycle with or without a nitrogen atom to be bonded via a nitrogen atom or an oxygen atom. The heterocycle may be a group selected from the group consisting of a lower alkyl group, a phenyl lower alkyl group or a lower alkanoyl group which may be substituted as a substituent.
Three may be substituted. An oxytocin antagonist comprising, as an active ingredient, at least one selected from the group consisting of a benzoheterocyclic compound represented by the formula: 2. The method according to claim 1, wherein the active ingredient is 5-dimethylamino-1-.
[4- (2-methylbenzoylamino) benzoyl]-
2,3,4,5-tetrahydro-1H-benzazepine
Or a salt thereof and 7-chloro-5-hydroxy-1- [2
-Methyl-4- (2-methylbenzoylamino) benzo
Yl] -2,3,4,5-tetrahydro-1H-benzo
At least selected from the group consisting of azepine or a salt thereof
The oxytocin antagonist according to claim 1, which is one kind.