Carbostyril derivatives and pharmaceutical composition containing the same

Abstract: Novel carbostyril derivatives of the formula: wherein X is O or S; Y is H or alkyl; R A is a group of the {wherein n is 1 or 2, A is alkylene, R¹ is benzoyl having optionally 1-3 substituents, R 2A is [R 3A is (i) alkoxy, (ii) substituted or unsubstitued 5- or 6-membered heterocylic group, (iii) alkenylthio, (iv) pyrrolidinyl-alkyl-S-, (v) pyrrolidinyl-alkyl-SO-, (vi) pyrrolidinyl-alkyl-SO₂-, (vii) -O-B-NR⁴R⁵ [B is alkylene having optionally OH, R⁴ is H, R⁵ is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-alkyl, etc., or R⁴ and R⁵ may together form a group of (R⁶ is substituted or unsubsituted amino)] or (viii) substituted alkoxy; m is 1 to 3]}, which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

Description: This invention relates to carbostyril derivatives which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a pharmaceutical composition containing said compound as the active ingredient. The carbostyril derivatives of this invention have the following formula: wherein X is oxygen or sulfur, Y is hydrogen or C 1-6 alkyl, R A is a group of the formula: wherein n is 1 or 2, A is a C 1-6 alkylene, and R 1 is benzoyl which phenyl ring may optionally have one to three substituents selected from C 1-6 alkoxy and amino having optionally a C 1-6 alkyl substituent, or R A is a group of the formula: wherein n is as defined above, and R 2A is a group of the formula: {wherein R 3A is i) C 1-6 alkoxy, ii) a 5- or 6-membered heterocylic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substituent selected from nitro and amino, iii) C 2-6 alkenylthio, iv) pyrrolidinyl-substituted C 1-6 alkylthio, v) pyrrolidinyl-substituted C 1-6 alkylsulfinyl, vi) pyrrolidinyl-substituted C 1-6 alkylsulfonyl, vii) a group of the formula: [wherein B is C 1-6 alkylene having optionally a hydroxy substituent, R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 akoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is amino which may optionally be substituted by C 1-6 alkanoyl having optionally one to three halogen substituents)], or viii) C 1-6 alkoxy having two substituents selected from aminocarbonyloxy having optionally a C 1-6 alkyl substituent and a group of the formula: (R 7 and R 8 are the same or different and are each hydrogen or C 1-6 alkyl), m is an integer of 1 to 3}, or R 2A is a group of the formula {wherein R 3B is a 7- to 10-membered monocyclic or dicyclic hetrocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substitutent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substitutent selected from nitro and amino}, the bond between 3- and 4-positions of the carbostyril ring is a single bond or a double bond, provided that when all of R 3A are C 1-6 alkoxy or when R 5 is C 1-6 alkanoyl, X is sulfur, and that when R 5 is C 2-6 alkenyl and X is oxygen, B is C 1-6 alkylene having a hydroxy substituent, and further that when R 3A is a heterocyclic group having C 1-6 alkyl or oxo substituent, the heterocyclic group is bound to the phenyl ring at a position other than the hetero atom, or a salt thereof. The preferred carbostyril derivatives of the present invention are compounds of the following formula: wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril ring are as defined in claim 1, R 3B is a 7- to 10-membered monocyclic or dicyclic hetrocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substitutent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substitutent selected from nitro and amino, or a salt thereof. The carbostyril derivatives of the formulae (1) and (1B) and their salts have excellent vasopressin antagonistic activities and vasodilating activity, hypotensive activity, activity for inhibiting saccharide release in liver, activity for inhibiting growth of mesangium cells, water diuretic activity, platelet agglutination inhibitory activity and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor and are used for the prophylaxis and treatment of hypertension, edema, ascites, heart failure, renal function disorder, vasopressin parasecretion syndrome (SIADH), hepatocirrhosis, hyponatremia, hypokaliemia, diabetic and circulation disorder. Each group in the above formulae (1) and (1B) includes specifically the following groups. The "C 1-6 alkoxy" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy and hexyloxy. The "C 1-6 alkyl" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl and hexyl. The "C 1-6 alkylene" includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene and hexamethylene. The "C 1-6 alkanoyl" includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl and hexanolyl. The "amino having optionally a C 1-6 alkyl substituent" includes an amino optionally having one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, 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 and N-methyl-N-hexylamino. The "benzoyl which phenyl ring may optionally have one to three substituents selected from C 1-6 alkoxy and amino having optionally a C 1-6 alkyl substituent" includes a benzoyl group which phenyl ring may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and an amino having optionally one or two substituents of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzoyl, 2-aminobenzoyl, 4-aminobenzoyl, 4-methylaminobenzoyl, 3-ethylaminobenzoyl, 2-(N-methyl-N-ethylamino)benzoyl, 3-(N-methyl-N-hexylamino)benzoyl, 4-dimethylaminobenzoyl, 4-dipentylaminobenzoyl, 2-isopropylaminobenzoyl, 3-butylaminobenzoyl, 4-(N-methyl-N-ethylamino)benzoyl, 2,3-bis(dimethylamino)benzoyl, 3,4-bis(methylamino)benzoyl, 3,4,5-tri(methylamino)benzoyl, 2,6-di(N-methyl-N-ethylamino)benzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenozyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-dimethoxybenzoyl, 3-ethoxy-4-methoxybenzoyl, 2,3-dimethoxybenzoyl, 2,4-dimethoxybenzoyl, 3,4-diethoxybenzoyl, 2,4-diethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, 3,5-dimethoxybenzoyl, 3,4-dipentyloxybenzoyl, 3,4,5-trimethoxybenozyl and 2-methoxy-4-dimethylaminobenzoyl. The "C 1-6 lower alkylene having optionally a hydroxy substituent includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms which has optionally a hydroxy substituent, for example, 2-hydroxytrimethylene, 2-hydroxytetramethylene, 2,3-dihydroxytetramethylene, 3-hydroxypentamethylene, 3-hydroxytetramethylene and 5-hydroxyhexamethylene. The "tricyclo[3.3.1.1]decanyl-substituted C 1-6 alkyl" includes a tricyclo[3.3.1.1]decanyl-substituted straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, tricyclo[3.3.1.1]decanylmethyl, 2-tricyclo[3.3.1.1]decanylethyl, 1-tricyclo[3.3.1.1]decanylethyl, 3-tricyclo[3.3.1.1]decanylpropyl, 4-tricyclo[3.3.1.1]decanylbutyl, 5-tricyclo[3.3.1.1]decanylpentyl, 6-tricyclo[3.3.1.1]decanylhexyl, 1,1-dimethyl-2-tricyclo[3.3.1.1]decanylethyl and 2-methyl-3-tricyclo[3.3.1.1]decanylpropyl. The "halogen-substituted C 1-6 alkyl" includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which has one to three halogen substituents, for example, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl and 5,6-dichlorohexyl. The "C 1-6 alkoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl" includes an alkoxycarbonyl-alkanoyloxy-alkyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms and the alkanoyloxy moiety is a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, and the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (2-methoxycarbonylacetyloxy)methyl, 2-(2-ethoxycarbonylacetyloxy)ethyl, 3-(3-propoxycarbonylpropionyloxy)propyl, 4-(4-butoxycarbonylbutyryloxy)butyl, 5-(5-pentyloxycarbonylpentanoyloxy)pentyl, 6-(6-tert-butyloxycarbonylhexanoyloxy)hexyl, 1,1-dimethyl-2-(2-hexyloxycarbonylacetyloxy)ethyl and 2-methyl-3-(3-ethoxycarbonylpropionyloxy)propyl. The "C 2-6 alkenyl" includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, for example, vinyl, allyl, 2-butenyl, 3-butenyl, 1-methylallyl, 2-pentenyl and 2-hexenyl. The "C 1-6 alkanoyl which may optionally have one to three halogen substituents" includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally have one to three substituents of a halogen atom, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, hexanoyl, 2,2,2-trifluoroacetyl, 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, 6-bromohexanoyl and 5,6-dibromohexanoyl. The "aminocarbonyloxy having optionally a C 1-6 alkyl substituent" includes an aminocarbonyloxy having optionally one to two substituetns of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyloxy, methylaminocarbonyloxy, ethylaminocarbonyloxy, propylaminocarbonyloxy, isopropylaminocarbonyloxy, butylaminocarbonyloxy, tert-butylaminocarbonyloxy, pentylaminocarbonyloxy, hexylaminocarbonyloxy, dimethylaminocarbonyloxy, diethylaminocarbonyloxy, dipropylaminocarbonyloxy, dibutylaminocarbonyloxy, dipentylaminocarbonyloxy, dihexylaminocarbonyloxy, N-methyl-N-ethylaminocarbonyloxy, N-ethyl-N-propylaminocarbonyloxy, N-methyl-N-butylaminocarbonyloxy and N-methyl-N-hexylaminocarbonyloxy. The "C 1-6 lower alkoxy having two substituents selected from an aminocarbonyloxy having optionally a C 1-6 alkyl substituent and a group of the formula: -NR 7 R 8 (R 7 and R 8 are the same or different and are each hydrogen or C 1-6 alkyl)" includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which has two substituents selected from an aminocarbonyloxy having one to two substituetns of a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a group of the formula: -NR 7 R 8 (R 7 and R 8 are the same or different and are each hydrogen atom or a straight chain or branched chain alkyl group having 1 to 6 carbon atoms), for example, 5-methylaminocarbonyloxy-6-diethylaminohexyloxy, 2-ethylaminocarbonyloxy-3-dimethylaminopropoxy, 3-propylaminocarbonyloxy-4-methylaminobutoxy, 5-butylaminocarbonyloxy-6-propylaminohexyloxy, 3-pentylaminocarbonyloxy-4-pentylaminobutoxy, 4-hexylaminocarbonyloxy-5-hexylaminopentyloxy, 1-(N-methyl-N-ethylaminocarbonyloxy)-2-diethylaminoethoxy and 5-methylaminocarbonyloxy-6-(N-methyl-N-ethylamino)hexyloxy. The "5- or 6-membered, or 7- to 10-membered monocyclic or dicyclic heterocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydrofuryl, thienyl, pyrrolyl, furyl, pyrazolyl, pyridyl, pyridazinyl, thiazolyl, oxazolyl, imidazolyl, pyrimidyl, pyrazyl, quinolyl, benzimidazolyl, indolyl, isoindolyl, cinnolyl, quinoxalyl, phthalazinyl, quinazolyl, benzo[b]furyl and benzo[b]thienyl. The above "heterocyclic group which may optionally have a substituent selected from alkyl, oxo, phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substituent selected from nitro and amino" includes the above-mentioned heterocyclic groups which may optionally have one to three substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, oxo, phenyl having optionally one to three substituents selected from a halogen atom and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms on the phenyl ring, and a phenylthio group having optionally one to three substituents selected from nitro and amino on the phenyl ring, for example, 2-ethyl-1-imidazolyl, 2-ethyl-4-methyl-1-imidazolyl, 3-methylpyrazolyl, 3,5-dimethylpyrazolyl, 1-methyl-2-imidazolyl, 1-oxothiomorpholino, 1,1-dioxothiomorpholino, 2-phenyl-1-imidazolyl, 3-phenyl-1-imidazolyl, 2-(2-nitrophenylthio)-1-imidazolyl, 2-(4-chlorophenyl)-1-imidazolyl, 2-(4-methoxyphenyl)-1-imidazolyl, 2-(2-aminophenylthio)-1-imidazolyl, 2-phenylthio-1-imidazolyl, 2-propyl-1-pyrrolidinyl, 3-butyl-2-pyrrolidinyl, 4-pentyl-1-piperidinyl, 1-hexyl-4-piperidinyl, 4-methyl-1-piperazinyl, 3,5-dimethyl-1-piperazinyl, 4-ethyl-2-piperazinyl, 2-methyl-4-morpholino, 3-ethyl-2-morpholinyl, 4-propyl-3-piperazinyl, 4-butyl-3-morpholinyl, 2-methyl-3-thiomorpholinyl, 3-ethyl-2-thiomorpholinyl, 3-pentyl-1-thiomorpholino, 4-hexyl-2-thiomorpholinyl, 3-methyl-2-tetrahydrofuryl, 2-methyl-3-thienyl, 1-methyl-3-pyrrolyl, 3-ethyl-1-pyrrolyl, 1-propyl-2-pyrrolyl, 3-methyl-2-furyl, 3-methyl-4-pyrazolyl, 4-methyl-1-pyrazolyl, 2-methyl-3-pyridyl, 3-ethyl-2-pyridyl, 2-methyl-4-pyridyl, 3-methyl-4-pyridazinyl, 2-methyl-4-thiazolyl, 2-ethyl-5-oxazolyl, 1,2,4-trimethyl-5-imidazolyl, 4-propyl-2-imidazolyl, 5-butyl-4-imidazolyl, 4-pentyl-2-imidazolyl, 2-hexyl-5-imidazolyl, 4-methyl-2-pyrimidyl, 2-propyl-3-pyrazinyl, 2-methyl-6-quinolyl, 2-methyl-5-benzimidazolyl, 5-ethyl-2-benzimidazolyl, 3-methyl-5-indolyl, 5-methyl-2-isoindolyl, 2-methyl-4-isoindolyl, 4-methyl-6-cinnolyl, 2-methyl-8-quinoxalyl, 1-methyl-7-phthalazyl, 7-methyl-6-quinazolyl, 6-methyl-3-benzo[b]furyl, 7-methyl-5-benzo[b]thienyl, 2-oxoquinolyl, 2-oxo-3-pyrrolidinyl and 3-oxo-2-piperazinyl. The "phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring" includes a phenyl group which may optionally have one to three substituents selected from a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms and halogen, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-pentyl-oxyphenyl, 2,4-dimethoxyphenyl, 4-hexyloxyphenyl, 3,4-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, 2-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 and 2-methoxy-3-chlorophenyl. The "phenylthio having optionally a substituent selected from nitro and amino" includes a phenylthio group having optionally one to three substituents selected from nitro and amino on the phenyl ring, for example, phenylthio, 2-nitrophenylthio, 3-nitrophenylthio, 4-nitrophenylthio, 2-aminophenylthio, 3-aminophenylthio, 4-aminophenylthio, 2,4-dinitrophenylthio, 2,4,6-trinitrophenylthio, 2,4-diaminophenylthio, 2,4,6-triaminophenylthio and 2-nitro-4-aminophenylthio. The "C 2-6 alkenylthio" includes a straight chain or branched chain alkenylthio group having 2 to 6 carbon atoms, for example, vinylthio, allylthio, 2-butenylthio, 3-butenylthio, 1-methylallylthio, 2-pentenylthio and 2-hexenylthio. The "pyrrolidinyl-substituted C 1-6 alkylthio" includes a pyrrolidinyl-substituted alkylthio group wherein the alkylthio moiety is a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, (1-pyrrolidinyl)methylthio, 2-(2-pyrrolidinyl)ethylthio, 1-(3-pyrrolidinyl)ethylthio, 3-(1-pyrrolidinyl)propylthio, 4-(1-pyrrolidinyl)butylthio, 5-(2-pyrrolidinyl)pentylthio, 6-(3-pyrrolidinyl)hexylthio, 1,1-dimethyl-2-(1-pyrrolidinyl)ethylthio and 2-methyl-3-(1-pyrrolidinyl)propylthio. The "pyrrolidinyl-substituted C 1-6 alkylsulfinyl" includes a pyrrolidinyl-substituted alkylsulfinyl group wherein the alkylsulfinyl moiety is a straight chain or branched chain alkylsulfinyl group having 1 to 6 carbon atoms, for example, (1-pyrrolidinyl)methylsulfinyl, 2-(2-pyrrolidinyl)ethylsulfinyl, 1-(3-pyrrolidinyl)ethylsulfinyl, 3-(1-pyrrolidinyl)propylsulfinyl, 4-(1-pyrrolidinyl)butylsulfinyl, 5-(2-pyrrolidinyl)pentylsulfinyl, 6-(3-pyrrolidinyl)hexylsulfinyl, 1,1-dimethyl-2-(1-pyrrolidinyl)ethylsulfinyl and 2-methyl-3-(1-pyrrolidinyl)propylsulfinyl. The "pyrrolidinyl-substituted C 1-6 alkylsulfonyl" includes a pyrrolidinyl-substituted alkylsulfonyl group wherein the alkylsulfonyl moiety is a straight chain or branched chain alkylsulfonyl group having 1 to 6 carbon atoms, for example, (1-pyrrolidinyl)methylsulfonyl, 2-(2-pyrrolidinyl)ethylsulfonyl, 1-(3-pyrrolidinyl)ethylsulfonyl, 3-(1-pyrrolidinyl)propylsulfonyl, 4-(1-pyrrolidinyl)butylsulfonyl, 5-(2-pyrrolidinyl)pentylsulfonyl, 6-(3-pyrrolidinyl)hexylsulfonyl, 1,1-dimethyl-2-(1-pyrrolidinyl)ethylsulfonyl and 2-methyl-3-(1-pyrrolidinyl)propylsulfonyl. The "C 1-6 alkylthio" includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio and hexylthio. The carbostyril derivatives of the present invention can be prepared by various processes, for example, by the processes shown in the following reaction schemes. wherein R is the same R A as defined above or a group of the formula: wherein n and R 3B are the same as defined above, and D is a group of the formula: -CH=CHR 14' (R 14' is C 1-6 alkoxy, phenyl or halogen), a group of the formula: (R 9 and R 10 are each C 1-6 alkyl), or a group of the formula: -C≡CH, and Y is hydrogen or C 1-6 alkyl. The cyclization reaction of the compound of the formula (2) is carried out in an appropriate solvent or without solvent in the presence of an acid. The acid includes any conventional inorganic acids and organic acids, for example, inorganic acids (e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, phosphorus pentoxide, polyphosphoric acid), Lewis acids (e.g. aluminum chloride, boron trifluoride, titanium tetrachloride), organic acids (e.g. formic acid, acetic acid, ethanesulfonic acid, p-toluenesulfonic acid), among which hydrochloric acid, hydrobromic acid and sulfuric acid are preferable. The acid is usually used in at least equivalent amount, preferably in an amount of 10 to 50 times by weight, as much as the amount of the compound (2). The solvent includes any conventional inert solvents, for example, water, lower alcohols (e.g. methanol, ethanol, propanol), ethers (e.g. dioxane, tetrahydrofuran), aromatic hydrocarbons (e.g. benzene, chlorobenzene, toluene), halogenated hydrocarbons (e.g. methylene chloride, chloroform, carbon tetrachloride), acetone, dimethylsulfoxide, dimethylformamide and hexamethylphosphoric triamide. The reaction is usually carried out at a temperature of from 0 to 200°C, preferably from room temperature to 150°C, for 5 minutes to 6 hours. The reduction of the compound of the formula (1a) is usually carried out under conventional conditions for the usual catalytic reduction. The catalyst includes metals such as palladium, palladium-carbon, platinum and Raney nickel. These metals are used in a conventional catalytic amount. The solvent used therein includes, for example, alcohols (e.g. methanol, ethanol, isopropanol), ethers (e.g. dioxane, tetrahydrofuran), aliphatic hydrocarbons (e.g. hexane, cyclohexane), esters (e.g. ethyl acetate) and fatty acids (e.g. acetic acid). The reduction reaction can be carried out under atmospheric pressure or under pressure, usually under atmospheric pressure to 19.6 bar (20 kg/cm 2 ), preferably atmospheric pressure to 9.8 bar (10 kg/cm 2 ). The reaction temperature is usually in the range of from 0°C to 150°C, prefarably from room temperature to 100°C. The dehydrogenation reaction of the compound of the formula (1b) is usually carried out in an appropriate solvent with an oxidizing agent. The oxidizing agent includes, for example, benzoquinones (e.g. 2,3-dichloro-5,6-dicyanobenzoquinone, chloranil (= 2,3,5,6-tetrachlorobenzoquinone)), halogenating agents (e.g. N-bromosuccinimide, N-chlorosuccinimide, bromine and hydrogenating catalysts (e.g. selenium oxide, palladium-carbon, palladium black, palladium oxide, Raney nickel). When a halogenating agent is used, it is used in a wide range of amount but is usually used in an amount of 1 to 5 moles, preferably 1 to 2 moles, to 1 mole of the compound (1b). When a hydrogenating catalyst is used, it is used in a catalytic amount as usual. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, methoxyethanol, dimethoxyethane), aromatic hydrocarbons (e.g. benzene, toluene, xylene, cumene), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride), alcohols (e.g. butanol, amyl alcohol, hexanol), polar protic solvents (e.g. acetic acid) and aprotic polar solvents (e.g. dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide). The reaction is usually carried out at a temperature of from room temperature to 300°C, peferably from room temperature to 200°C, for 1 to 40 hours. wherein R and Y are the same as defined above. The cyclization reaction of the compound (3) is carried out in an appropriate solvent in the presence of a condensation agent. The condensation agent includes, for example, Lewis acids, such as phosphorus pentoxide, hydrogen fluoride, sulfuric acid, polyphosphoric acid, aluminum chloride and zinc chloride. The solvent includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, 1,2-dichloroethane), ethers (e.g. diethyl ether, dioxane), aromatic hydrocarbons (e.g. nitrobenzene, chlorobenzene). The condensation agent is usually used in an amount of 1 to 10 moles, peferably 3 to 6 moles, to 1 mole of the compound (3). The reaction is usually carried out at a temperature of 50°C to 250°C, peferably 70°C to 200°C, for 20 minutes to 6 hours. wherein R, Y and the bond between 3- and 4-positions of the carbonstyril nucleus are the same as defined above. The cyclization reaction of the compound (4) is carried out in an appropriate solvent or without using a solvent in the presence of an acid. The acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, nitric acid, polyphosphoric acid), and organic acids (e.g. p-toluenesulfonic acid, ethanesulfonic acid, trifluoroacetic acid). The solvent includes any conventional solvents unless they affect on the reaction, for example, water, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve), pyridine, acetone, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), ethers (e.g. diethyl ether, tetrahydrofuran, dimethoxyethane, diphenyl ether), esters (e.g. methyl acetate, ethyl acetate), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide), or a mixture of these solvents. The reaction is usually carried out at a temperature of from -20°C to 150°C, preferably from 0°C to 150°C, for 5 minutes to 30 hours. wherein R, X, Y and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and X 1 is a halogen atom. The reaction of the compound of the fomrula (5) and the compound of the formula (6) is usually carried out in an appropriate inert solvent in the presence or absence of a basic compound. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene), alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve), pyridine, acetone, N-methylpyrrolidone, dimethylsulfoxide, dimethylformamide and hexamethylphosphoric triamide. The basic compound includes, for example, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride and triethylamine. The amounts of the compound (5) and the compound (6) are not critical, but the compound (6) is usually used at least in equimolar amount, preferably in an amount of 1 to 5 moles to 1 mole of the compound (5). The reaction is usually carried out at a temperature of from room temperature to 200°C, preferably 100°C to 180°C, for 3 to 30 hours. In the above reaction, a copper powder may also be used as a catalyst, by which the reaction can proceed advantageously. wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R 2 is the same as R 2A as mentioned above. wherein R 1 , X, Y, A, n and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above. The process of Reaction Schemes-5A and -5B is carried out by reacting a carbostyril derivative of the formula (1d) or (1d') and a carboxylic acid compound of the formula (7) or (7a) by a conventional amido bond producing reaction. The amido bond producing reaction can be carried out under the conditions for the conventional amido bond producing reaction, for example, (a) a mixed acid anhydride process, i.e. a process of reacting the carboxylic acid compound (7) or (7a) with an alkyl-halocarboxylic acid to form a mixed acid anhydride and reacting the resultant with the amine compound (1d) or (1d'), (b) an activated ester process, i.e. a process of converting the carboxylic acid compound (7) or (7a) into an activated ester, such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, and reacting the resultant with the amine compound (1d) or (1d'), (c) a carbodiimide process, i.e. a process of condensing the carboxylic acid compound (7) or (7a) and the amine compound (1d) or (1d') in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, (d) other processes, i.e. a process of converting the carboxylic acid compound (7) or (7a) into a carboxylic anhydride by treating it with a dehydrating agent such as acetic anhydride, and reacting the resultant with the amine compound (1d) or (1d'); a process of reacting an ester of the carboxylic acid compound (7) or (7a) with a lower alcohol and the amine compound (1d) or (1d') at a high temperature under high pressure; a process of reacting an acid halide compound of the carboxylic acid compound (7) or (7a), i.e. a carboxylic acid halide, with the amine compound (1d) or (1d'). The mixed acid anhydride used in the above mixed acid anhydride process is obtained by the known Schötten-Baumann reaction, and the reaction product is used without isolation from the reaction mixture for the reaction with the amine compound (1d) or (1d') to give the desired compound of the formula (1e) or (1e'). The Schötten-Baumann reaction is usually carried out in the presence of a basic compound. The basic compound is any conventional compounds used for the Schötten-Baumann reaction and includes, for example, organic basic compounds such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU) and 1,4-diazabicyclo[2.2.2]octane (DABCO), and inorganic basic compounds such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate and sodium hydrogen carbonate. The reaction is usually carried out at a temperature of from -20°C to 100°C, preferably from 0°C to 50°C, for 5 minutes to 10 hours, preferably 5 minutes to 2 hours. The reaction of the thus obtained mixed acid anhydride with the amine compound (1d) or (1d') is usually carried out at a temperature of from -20°C to 150°C, preferably 10°C to 50°C, for 5 minutes to 10 hours, preferably 5 minutes to 5 hours. The mixed acid anhydride process is usually carried out in an appropriate solvent. The solvent is any conventional solvents which are usually used in the mixed acid anhydride process and includes, for example, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane), esters (e.g. methyl acetate, ethyl acetate), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide), or a mixture of these solvents. The alkylhalocarboxylic acid used in the mixed acid anhydride process includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate and isobutyl chloroformate. In said process, the carboxylic acid compound (7) or (7a), the alkylhalocarboxylic acid and the amine (1d) or (1d') are usually used in each equimolar amount, but preferably, the alkylhalocarboxylic acid and the carboxylic acid compound (7) or (7a) are used each in an amount of 1 to 1.5 mole to 1 mole of the amine (1d) or (1d'). Among the above other processes (d), in case of the process of reacting the carboxylic acid halide with the amine compound (1d) or (1d'), the reaction is usually carried out in the presence of a basic compound in an appropriate solvent. The basic compound is any conventional compounds and includes, in addition to the basic compounds used for the above-mentioned Schötten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium hydride and potassium hydride. The solvent includes, in addition to the solvents used for the above-mentioned mixed acid anhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve), acetonitrile, pyridine and acetone. The amount of the amine compound (1d) or (1d') and the carboxylic acid halide is not critical, but the carboxylic acid halide is usually used at least in equimolar amount, preferably 1 to 5 moles to 1 mole of the amine compound (1d) or (1d'). The reaction is usually carried out at a temperature of from -20°C to 180°C, preferably from 0°C to 150°C, for 5 minutes to 30 hours. The amido bond producing reaction in the above Reaction Schemes-5A and -5B may also be carried out by reacting the carboxylic acid compound (7) or (7a) and the amine (1d) or (1d') in the presence of a condensation agent such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, bis(2-oxo-3-oxazolidinyl)phosphinic chloride. The reaction is usually carried out in the presence of the solvent and basic compound as used in the above reaction of the carboxylic acid halide and the amine (1d) or (1d') at a temperature of from -20°C to 150°C, preferably 0°C to 100°C, for 5 minutes to 30 hours. The condensation agent and the carboxylic acid compound (7) or (7a) are used at least in equimolar amount, preferably 1 to 2 moles, to 1 mole of the amine (1d) or (1d'). wherein X, Y, n, R 3A , X 1 , B, A, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R 4' is hydrogen, R 5a is tricyclo[3.3.1.1]decanyl tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 alkoxycarbonylC 2-6 alkanoyloxy-C 1-6 alkyl, or C 2-6 alkenyl, and p' and p" are each an integer of 1 to 3, provided that p + p' and p + p" are each an integer not more than 3. wherein X, Y, n, X 1 , A, and the bond between 3- and 4-positions of carbostyril nucleus are the same as defined above, and R 11 is an amino being optionally substituted by C 1-6 alkoxy or C 1-6 alkyl, R 12 is C 1-6 alkyl, R 13 is hydrogen or C 1-6 alkyl, and p' and p" are each an integer of 1 to 3, provided that p + p' and p + p" are each an integer not more than 3. wherein X, Y, n, R 3A , X 1 , R 12 , R 13 , and the bond between 3-and 4-positions of carbostyril nucleus are the same as defined above, and p' and p" are each an integer of 1 to 3, provided that p + p' and p + p" are each an integer not more than 3. The reaction of the compound (1f) and the compound (7b) in Reaction Scheme-6A, the reaction of the compound (1h) and the compound (8) in Reaction Scheme-6B, and the reaction of the compound (1h') and the compound (8) in Reaction Scheme-6C are usually carried out in an inert solvent in the presence or absence of a basic compound. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene), ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride), acetic acid, ethyl acetate, acetone, acetonitrile, dimethylsulfoxide, dimethylformamide and hexamethylphosphoric triamide. The basic compound includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide), sodium hydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodium methoxide, sodium ethoxide), and organic basic compounds (e.g. pyridine, ethyldiisopropylamine, dimethylaminopyridine; triethylamine, 1,5-diazabicyclo[4.3.0]nonene-(5) (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO)). The ratio of the compound (7b) or (8) to the compound (1f), (1h) or (1h') is not critical, but the compound (7b) or (8) is usually used at least in equivalent amount, preferably 1 to 5 moles, to 1 mole of the compound (1f), (1h) or (1h'). The reaction is usually carried out at a temperature of from 0°C to 200°C, preferably from 0°C to 170°C, for 30 minutes to 30 hours. Moreover, the compounds (1i) and (1i') wherein R 12 is a C 1-6 alkyl can also be obtained by reacting the compound (1h) or (1h') with a compound of the formula: R 14 -CO-R 15 wherein R 14 and R 15 are each hydrogen or C 1-6 alkyl, respectively. The reaction is usually carried out in an appropriate solvent or without solvent in the presence of a reducing agent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol), acetonitrile, formic acid, acetic acid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran), aromatic hydrocarbons (e.g. benzene, toluene, xylene), or a mixture of these solvents. The reducing agent includes, for example, formic acid, fatty acid alkali metal salts (e.g. sodium formate), hydrogenating reducing agents (e.g. sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride) and catalytic reducing agents (e.g. palladium black, palladium-carbon, platinum oxide, platinum black, Raney nickel). When formic acid is used as the reducing agent, the reaction is usually carried out at a temperature of from room temperature to 200°C, peferably 50°C to 150°C, for 1 to 10 hours. The formic acid is usually used in a large excess amount to the compound (1h) or (1h'). When a hydrogenating reducing agent is used, the reaction is usually carried out at a temperature of -30°C to 100°C, preferably 0°C to 70°C, for 30 minutes to 12 hours. The reducing agent is usually used in an amount of 1 to 20 moles, preferably 1 to 6 moles, to 1 mole of the compound (1h) or (1h'). When lithium aluminum hydride is used as the reducing agent, it is preferable to use a solvent selected from ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, diglyme) and aromatic hydrocarbons (e.g. benzene, toluene, xylene). When a catalytic reducing agent is used, the reaction is usually carried out under atmospheric pressure to 19.6 bar (20 atm), preferably atmospheric pressure to 9.8 bar (10 atm) under hydrogen atmosphere or in the presence of a hydrogen donor (e.g. formic acid, ammonium formate, cyclohexene, hydrazine hydrate) at a temperature of -30°C to 100°C, preferably 0°C to 60°C, for 1 to 12 hours. The catalytic reducing agent is usually used in an amount of 0.1 to 40 % by weight, preferably 1 to 20 % by weight, of the amount of the compound (1h) or (1h'). The compound (9) is usually used at least in equivalent amount, preferably equivalent to a large excess amount, to the compound (1h) or (1h'). wherein X, Y, p, R 3A , n, R 4 , R 5 , p', p", B, X 1 , and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above. The reaction of the compound (1j) and the compound (10) is carried out under the same conditions as in the reaction of the compound (1f) and the compound (7b) in the above Reaction Scheme-6A. wherein R, Y and X 1 are the same as defined above. The cyclization reaction of the compound (1ℓ) is so-called Friedel Craft reaction and is usually carried out in an appropriate solvent in the presence of a Lewis acid. The solvent includes any conventional solvent which is usually used in this kind of reaction, for example, carbon disulfide, nitrobenzene, chlorobenzene, dichloromethane, dichloroethane, trichloroethane and tetrachloroethane. The Lewis acid includes any conventional acid, for example, aluminum chloride, zinc chloride, iron chloride, tin chloride, boron tribromide, boron trifluoride and conc. sulfuric acid. The amount of Lewis acid is not critical but is usually in the range of 2 to 6 moles, preferably 3 to 4 moles, to 1 mole of the compound (1ℓ). The reaction temperature is usually in the range of 20°C to 200°C, preferably 40°C to 180°C. The reaction period of time may vary depending on the kinds of the starting compound, catalyst and reaction temperature, but is usually in the range of 0.5 to 6 hours. Besides, sodium chloride may be added to the reaction system in order to proceed the reaction advantageously. wherein X, Y, R 3A , n, p, p', p", and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R 3a is C 2-6 alkenyloxy, R 3b is oxilanyl- substituted C 1-6 alkoxy, R 3c is C 1-6 alkoxy having a substituent selected from a group of the formula: (R 4 and R 5 are as defined above) and hydroxy, and p"' is an integer of 1 to 3, provided that p + p"' is not more than 3. The reaction of converting the compound (11) into the compound (12) is carried out in an appropriate solvent in the presence of an oxidizing agent. The solvent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid), alcohols (e.g. methanol, ethanol), halogenated hydrocarbons (e.g. chloroform, dichloromethane), or a mixture of these solvents. The oxidizing agent includes, for example, peracids (e.g. performic acid, peracetic acid, trifluoro-peracetic acid, perbenzoic acid, m-chloro-perbenzoic acid, o-carboxy-perbenzoic acid), hydrogen peroxide, sodium metaperiodate, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate and lead salts (e.g. lead tetraacetate). The oxidizing agent is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the starting compound. The above reaction is usually carried out at a temperature of 0°C to 40°C, preferably from 0°C to room temperature, for 1 to 15 hours. The reaction of the compound (12) and the compound (13) is carried out under the same conditions as in the reaction of the compound (1f) and the compound (7b) in the above Reaction Scheme-6A. The starting compound (2) can be prepared, for example, by the processes as shown in the following Reaction Schemes-10 and -11. wherein R 2 , Y, n and D are the same as defined above. The reaction of the compound (15) and the compound (16) is carried out under the same conditions as in the reaction of the compound (1h) and the compound (9) in the above Reaction Scheme-6B. The reaction of the compound (17) and the compound (18) is carried out under the same conditions as in the reaction of the compound (1d) and the compound (7) in the above Reaction Scheme-5. wherein R 1 , A, Y, n, and D are the same as defined above. The reaction of the compound (19) and the compound (18) is carried out under the same conditions as the above reaction of the compound (17) and the compound (18). The starting compound (4) can be prepared, for example, by the process of the following Reaction Schem-12. wherein R 2 , Y, and n are the same as defined above. The reaction of the compound (21) and the compound (22) is carried out under the same conditions as in the reaction of the compound (15) and the compound (16) in the above Reaction Scheme-10. The starting compound (1ℓ) can be prepared, for example, by the process of the following Reaction Scheme-13. wherein R, Y and X 1 are as defined above. The reaction of the compound (23) and the compound (24) is carried out under the same conditions as in the reaction of the compound (17) and the compound (18) in the above Reaction Scheme-10. wherein R, Y and X 1 are the same as defined above, and R 16 is phenyl and R 17 is C 1-6 alkoxycarbonyl. The reaction of the compound (25) and the compound (26) is carried out in an appropriate solvent in the presence of a basic compound. The basic compound includes inorganic bases (e.g. sodium metal, potassium metal, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate), metal alcoholates (e.g. sodium methylate, sodium ethylate, potassium t-butoxide), alkyl or aryl lithiums or lithium amides (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide), organic bases (e.g. pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline). The solvent includes any solvent which does not affect on the reaction, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme), aromatic hydrocarbons (e.g. benzene, toluene, xylene), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane), amines (e.g. pyridine, N,N-dimethylaniline), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide and alcohols (e.g. methanol, ethanol, isopropanol). The reaction is usually carried out at a temperature of -80°C to 150°C, preferably -80°C to 120°C, for 0.5 to 15 hours. The cyclization reaction of the compound (27) is carried out in the presence of a catalytic reducing agent and in the presence or absence of a basic compound or an acid, preferably in the presence of an acid, in an appropriate solvent. The basic compound includes, for example, organic bases (e.g. triethylamine, trimethylamine, pyridine, dimethylaniline, N-methylmorpholine, DBN, DBU, DABCO), and inorganic bases (e.g. potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, potassium hydrogen carbonate, sodium hydrogen carbonate), and the acid includes, for example, inorganic acids (e.g. hydrochloric acid, sulfuric acid, phosphoric acid), organic acids (e.g. acetic acid), or a mixture of these acids. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve), pyridine, acetone, halogenated hydrocarbons (e.g. methylene chloride, chloroform, dichloroethane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), ethers (e.g. tetrahydrofuran, diethyl ether, dimethoxyethane), esters (e.g. methyl acetate, ethyl acetate), N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, or a mixture of these solvents. The catalytic reducing agent includes the same catalysts as used in the reduction reaction of the compound (1a) in the above Reaction Scheme-1. The reaction is usually carried out under atmospheric pressure to 19.6 bar (20 kg/cm 2 ), preferably atmospheric pressure to 9.8 bar (10 kg/cm 2 ), at a temperature of 0°C to 200°C, preferably from room temperature to 150°C, for 1 to 10 hours. The catalytic reducing agent is preferably used in an amount of 0.02 to 1 part by weight to 1 part by weight of the compound (27). wherein R 2 , Y and n are as defined above. The reaction of the compound (28) and the compound (16) is carried out under the same conditions as in the reaction of the compound (15) and the compound (16) in the above Reaction Scheme-10. The reaction of converting the compound (29) into the compound (25a) is carried out in an appropriate solvent or without solvent in the presence of an oxidizing agent. The solvent includes the above-mentioned aromatic hydrocarbons, lower alcohols, halogenated hydrocarbons, ethers, polar solvents (e.g. dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide). The oxidizing agent includes acetic anhydride-dimethylsulfoxide, phosphorus pentoxide-dimethylsulfoxide, sulfur trioxide,pyridine complex-dimethylsulfoxide, dicyclohexylcarbodiimidedimethylsulfoxide, oxalyl chloride-dimethylsulfoxide, chromic acid, chromic acid complexes (e.g. chromic acid-pyridine complex, chromic acid-2-pyridine complex) and manganese dioxide. When oxalyl chloride-dimethylsulfoxide is used as the oxidizing agent, there may be added to the reaction system the basic compound as used in the reaction of the compound (1d) and the carboxylic halide in the above Reaction Scheme-5. The reaction is usually carried out at a temperature of 0°C to 150°C, preferably from room temperature to 100°C, for 1 to 30 hours. The oxidizing agent is usually used in an amount of 1 to 20 moles, preferably 1 to 15 moles, to 1 mole of the compound (29). wherein R, X, Y and n are the same as defined above. The reaction of the compound (30) and the compound (31) is carried out under the same conditions as in the reaction of the compound (5) and the compound (6) in the above Reaction Scheme-4. In this reaction, copper monoxide may be added to the reaction system in order to proceed the reaction advantageously. The reaction of converting the compound (32) into the compound (29) can be carried out by reducing the compound (32). The reduction reaction is preferably carried out by using a hydrogenating reducing agent. The hydrogenating reducing agent includes, for example, lithium aluminum hydride, sodium borohydride and diborane. The reducing agent is usually used at least in equimolar amount, preferably 1 to 15 moles, to 1 mole of the starting compound. The reducing reaction is usually carried out in an appropriate solvent, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol), ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme), or a mixture of these solvents, at a temperature of -60°C to 150°C, preferably -30°C to 100°C, for 10 minutes to 5 hours. When lithium aluminum hydride or diborane is used as the reducing agent, it is preferable to use anhydrous solvents such as tetrahydrofuran, diethyl ether, diisopropyl ether and diglyme. wherein R 3A , X, Y, n, p, p', p", X 1 , and the bond between 3-and 4-positions of the carbostyril nucleus are the same as defined above, and R 18 is C 1-6 alkyl, a group of the formula: (B, R 4 and R 5 are the same as defined above), or C 1-6 alkyl having two substituents selected from an aminocarbonyloxy having optionally C 1-6 alkyl and a group of the formula: (R 7 and R 8 are the same as defined above). The reaction of the compound (33) and the compound (34) is carried out under the same conditions as in the reaction of the compound (1f) and the compound (7b) in the above Reaction Scheme-6A. In said reaction, an alkali metal halide (e.g. sodium iodide, potassium iodide) may be added to the reaction system. wherein R 3A , X, Y, n, p, p', p", B, R 4 , X 1 , and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R 5b is hydroxy-substituted C 1-6 alkyl, R 5c is C 1-6 alkoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl, and R 19 is C 1-6 alkoxycarbonyl-C 2-6 alkanoyl. The reaction of the compound (35) and the compound (36) is carried out under the same conditions as in the reaction of the compound (1f) and the compound (7b) in the above Reaction Scheme-6A. wherein X, Y, R 3A , p, p', p", n, and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R 20 is C 1-6 alkoxy having two substituents selected from hydroxy and a group of the formula: (R 7 and R 8 are the same as defined above), R 21 is C 1-6 alkyl, and R 22 is an aminocarbonyloxy having optionally a C 1-6 alkyl substituent, or a group of the formula: (R 7 and R 8 are the same as defined above). The reaction of the compound (37) and the compound (38) is carried out in the presence or absence, preferably absence, of a basic compound in an appropriate solvent or without using any solvent. The solvent and basic compound used in the above reaction are the same solvents and basic compounds as used in the reaction of the amine (1d) and the carboxylic acid halide in the above Reaction Scheme-5. The compound (38) is usually used in an amount of 1 to 5 moles, preferably 1 to 3 moles, to 1 mole of the compound (37). The reaction is usually carried out at a temperature of 0 to 200°C, preferably room temperature to 150°C, for 5 minutes to 30 hours. In the reaction, a boric compound (e.g. borone trifluoride-ethyl etherate) may be added to the reaction system. wherein X, Y, R 3A , B, p, p', p", and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above, and R 6a is amino, R 6b is amino substituted by C 1-6 alkanoyl having optionally 1 to 3 halogen substituents, and R 23 is C 1-6 alkanoyl having optionally 1 to 3 halogen substituents. The reaction of the compound (1p) and the compound (39) is carried out under the same conditions as in the reaction of the compound (1d) and the compound (7) in the above Reaction Scheme-5. The reaction of the compound (1p) and the compound (40) is carried out without solvent or in an appropriate solvent in the presence or absence, preferably presence, of a basic compound. The solvent includes, for example, the above-mentioned aromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol), dimethylformamide, dimethylsulfoxide, and further halogenated hydrocarbons (e.g. chloroform, methylene chloride), acetone and pyridine. The basic compound includes, for example, tertiary amines (e.g. triethylamine, pyridine), sodium hydroxide, potassium hydroxide and sodium hydride. The above reaction may also be carried out in a solvent (e.g. acetic acid) in the presence of a mineral acid (e.g. sulfuric acid). The compound (40) is usually used in an equimolar amount or more, preferably 1 to 10 moles, to 1 mole of the compound (1p). The above reaction is usually carried out at a temperature of 0 to 200°C, preferably 0 to 150°C, for 0.5 to 15 hours. The hydrolysis of the compound (1q) can be carried out in an appropriate solvent or without solvent in the presence of an acid or a basic compound. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol), ketones (e.g. acetone, methyl ethyl ketone), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether), fatty acids (e.g. acetic acid, formic acid), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid) and organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acids). The basic compound includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate) and metal hydoxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide). The reaction is usually carried out at a temperature of from room temperature to 200°C, preferably from room temperature to 150°C, for 0.5 to 25 hours. wherein R, Y and the bond between 3- and 4-positions of the carbostyril nucleus are the same as defined above. The reaction of the compound (1c) and phosphorus pentasulfide or Lawesson's reagent (as mentioned in Reference Example 1 hereinafter) is usually carried out in an inert solvent such as aromatic hydrocarbons (e.g. benzene, toluene, xylene, chlorobenzene), ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), halogenated hydrocarbons (e.g. methylene chloride, chloroform), dimethylsulfoxide and hexamethylphosphoric triamide. The phosphorus pentasulfide or Lawesson's reagent is usually used in an amount of 0.2 mole to large excess amount, preferably 0.4 to 2 moles, to 1 mole of the compound (1c). The reaction is usually carried out at a temperature of from room temperature to 200°C, preferably 50 to 150°C, for 0.5 to 50 hours. The starting compounds (1d), (1f), (1j), (1l), (33), (35) and (37) can readily be prepared by various processes as shown in the above Reaction Schemes-1 to -5 by using appropriate starting materials. In the case of the compounds of the formula (1) wherein R 3 is thiomorpholino or 1-oxothiomorpholino; or pyrrolidinyl-substituted C 1-6 alkylthio or pyrrolidinyl-substituted C 1-6 alkylsulfinyl can be converted into the corresponding compounds of the formula (1) wherein R 3 is 1-oxo- or 1,1-dioxothiomopholino or 1,1-dioxothiomorpholino; or pyrrolidinyl-substituted C 1-6 alkyl-sulfinyl or -sulfonyl, or pyrrolidinyl-substituted C 1-6 alkylsulfonyl, respectively by oxidation thereof. The above oxidation reaction is carried out in an appropriate solvent in the presence of an oxidizing agent. The solvent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid), alcohols (e.g. methanol, ethanol), halogenated hydrocarbons (e.g. chloroform, dichloromethane), or a mixture of these solvents. The oxidizing agent includes, for example, peracids (e.g. performic acid, peracetic acid, trifluoro-peracetic acid, perbenzoic acid, m-chloro-perbenzoic acid, o-carboxy-perbenzoic acid), hydrogen peroxide, sodium metaperiodate, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate) and lead salts (e.g. lead tetraacetate). The oxidizing agent is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of the starting compound. In case of converting thiomorpholino into 1,1-dioxothiomorpholino or converting pyrrolidinyl-substituted C 1-6 alkylthio into pyrrolidinyl-substituted C 1-6 alkylsulfonyl, the oxiding agent is usually used in an amount of at least two moles, peferably 2 to 4 moles, to 1 mole of the starting compound. The above reaction is usually carried out at a temperature of -40°C to 40°C, preferably from -40°C to room temperature, for 10 minutes to 10 hours. In the case of the compounds of the formula (1) wherein R 3 is a phenylthio having at least one nitro substituent, the compounds can be subjected to a reduction reaction to convert into the corresponding compounds wherein R 3 is a phenylthio having at least one amino substituent. The reduction reaction can be carried out, for example, (1) by reducing them in an appropriate solvent with a catalytic reducing agent, or (2) by reducing them in an appropriate inert solvent with a reducing agent, such as a combination of a metal or metal salt and an acid, or a metal or metal salt and an alkali metal hydroxide, sulfide and ammonium salt. In the case of reduction using a catalytic reducing agent (1), the solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol), hydrocarbons (e.g. hexane, cyclohexane), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether), esters (e.g. ethyl acetate, methyl acetate) and aprotic polar solvent (e.g. N,N-dimethylformamide). The catalytic reducing agent includes, for example, palladium, palladium black, palladium-carbon, platinum, platinum oxide, copper chromite and Raney nickel. The catalyst is usually used in an amount of 0.02 to 1 part by weight to 1 part by weight of the starting compound. The reaction is usually carried out at a temperature of -20°C to 150°C, preferably from 0°C to 100°C, under a hydrogen pressure of 0.98 to 9.8 bar (1 to 10 atm), for 0.5 to 10 hours. In the case of the reduction (2), the reducing agent includes a combination of iron, zinc, tin or stannous chloride with a mineral acid (e.g. hydrochloric acid, sulfuric acid), or of iron, ferrous sulfate, zinc or tin with an alkali metal hydroxide (e.g. sodium hydroxide), a sulfide (e.g. ammonium sulfide), aqueous ammonia, or an ammonium salt (e.g. ammonium chloride). The inert solvent includes, for example, water, acetic acid, methanol, ethanol and dioxane. The conditions of the reduction reaction are determined depending on the kinds of the reducing agent, for example, in case of a combination of stannous chloride and hydrochloric acid, it is advantageously carried out at a temperature of 0°C to room temperature for 0.5 to 10 hours. The reducing agent is usually used in an amount of at least 1 mole, preferably 1 to 5 moles, to 1 mole of the starting compound. In case of the compounds of the formula (i) wherein R 3 is a heterocyclic group where the substituent on at least one nitrogen atom is hydrogen atom, the compounds can be converted into the corresponding compounds wherein R 3 is a heterocyclic group where the substituent on at least one nitrogen is C 1-6 alkyl by reacting them with a compound of the formula: R 18 X 1 wherein R 18 and X 1 are the same as defined above, or a compound of the formula: R 14 -CO-R 15 wherein R 14 and R 15 are the same as defined above, under the same conditions as in the reaction of the compound (1f) and the compound (7b) in the above Reaction Scheme-6A or in the reaction of the compound (1h) and the compound (8) in the above Reaction Scheme-6B. Among the active compounds (1) of this invention, the compounds having an acidic group can easily be converted into salts by treating with a pharmaceutically acceptable basic compound. The basic compound includes, for example, metal hydroxides such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, alkali metal carbonates or hydrogen carbonates such as sodium carbonate, sodium hydrogen carbonate, and alkali metal alcoholates such as sodium methylate, potassium ethylate. Besides, among the active compounds (1) of this invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids such as sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, and organic acids such as acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, citric acid, succinic acid, benzoic acid. Besides, the compounds (1) of this invention include stereoisomers and optical isomers, and these isomers are also useful as the active ingredient in this invention. The compounds of this invention thus obtained can easily be isolated and purified by conventional isolation methods. The isolation methods are, for example, distillation method, recrystallization method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromtography, preparative thin layer chromatography and extraction with a solvent. The compounds and their salts of this invention are useful as a vasopressin antagonist and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional dilutents or carriers such as fillers, thickening agents, binders, wetting agents, disintegrators, surfactants and lubricants. The pharmaceutical preparations may be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used carriers such as vehicles (e.g. lactose, white sugar, sodium chloride, glucose, urea, starches, calcium carbonate, kaolin, crystalline cellulose, silicic acid), binders (e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone), disintegrators (e.g. dry starch, sodium arginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose), disintegration inhibitors (e.g. white sugar, stearin, cacao butter, hydrogenated oils), absorption promoters (e.g. quaternary ammonium base, sodium laurylsulfate), wetting agents (e.g. glycerin, starches), adsorbents (e.g. starches, lactose, kaolin, bentonite, colloidal silicates) and lubricants (e.g. purified talc, stearates, boric acid powder, polyethylene glycol). Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. In the preparation of pills, the carriers include vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc), binders (e.g. gum arabic powder, tragacanth powder, gelatin, ethanol) and disintegrators (e.g. laminaran, agar). In the preparation of suppositories, the carriers include, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin and semi-synthetic glycerides. Capsules can be prepared by charging a mixture of the compound of this invention with the above carriers into hard gelatin capsules or soft capsules in a usual manner. In the preparation of injections, the solutions, emulsions or suspendions are sterilized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol and polyoxyethylene sorbitan fatty acid esters. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agents, preservatives, perfumes, flavors, sweeting agents, and other medicaments, if required. The amount of the active compound of this invention (active ingredient) to be incorporated into the anti-vasopressin preparations is not specified but may be selected from a broad range, but usually, it is preferably in the range of 1 to 70 % by weight, more preferably 5 to 50 % by weight. The anti-vasopressin preparation of this invention may be administered in any method, and suitable method for administration may be determined in accordance with various forms of preparation, ages, sexes and other conditions of the patients and the degree of severity of diseases. For instance, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. The injections are intraveneously administered alone or together with a conventional auxiliary liquid (e.g. glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route. The dosage of the anti-vasopressin agent of this invention may be selected in accordance with the usage, ages, sexes and other conditions of the patients and the degre of severity of the diseases, but is usually in the range of 0.6 to 50 mg of the active compound of this invention per 1 kg of body weight of the patient per day. The active compound is preferably contained in an amount of 10 to 1000 mg per the dosage unit. Examples The present invention is illustrated by the following Preparations of anti-vasopressin agent, Reference Examples of processes for preparing the starting compounds to be used for preparing the active compounds, Examples of processes for preparing the active compounds, and Experiments of the activities of the active compounds of this invention. Preparation 1 Film coated tablets are prepared from the following components. The active component of this invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and ethanol to give film coated tablets. Preparation 2 Tablets are prepared from the following components. The active compound of this invention, citric acid, lactose, dicalcium phosphate, Pullonic F-68 and sodium laurylstearate are mixed. The mixture is screened with No. 60 screen and is granulated with an alcohol solution containing polyvinylpyrrolidone, carbowax 1500 and 6000. If required, an alcohol is added thereto so that the powder mixture is made a paste-like mass. Corn starch is added to the mixture and the mixture is continuously mixed to form uniform particles. The resulting particles are passed through No. 10 screen and entered into a tray and then dried in an oven at 100°C for 12 to 14 hours. The dried particles are screened with No. 16 screen and thereto are added dry sodium laurylsulfate and dry magnesium stearate, and the mixture is tabletted to form the desired shape. The core tablets thus prepared are vanished and dusted with talc in order to guard from wetting. Undercoating is applied to the core tablets. In order to administer the tablets orally, the core tablets are vanished several times. In order to give round shape and smooth surface to the tablets, further undercoating and coating with lubricant are applied thereto. The tablets are further coated with a coloring coating material until the desired colored tablets are obtained. After drying, the coated tablets are polished to obtain the desired tablets having uniform gloss. Preparation 3 An injection preparation is prepared from the following components. Components Amount 1-{1-[4-(5-Methylaminocarbonyloxy-6-dimethylaminohexyloxy)benzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril 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 parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water of half volume of the above with stirring at 80°C. The solution thus obtained is cooled to 40°C, and the active compound of this invention and further polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. To the solution is added distilled water for injection to adjust to the desired volume, and the solution is sterilized by filtering with an appropriate filter paper to give an injection preparation. Reference Example 1 1-(4-Piperidinyl)-3,4-dihydrocarbostyril hydrochloride (5 g) and a Lawesson's Reagent * ) (3.8 g) are dispersed in toluene (20 ml), and the mixture is refluxed for 40 hours. To the reaction mixture is added water, and the mixture is acidified with hydrochloric acid, and the organic layer is separated. The aqueous layer is basified with sodium hydroxide, extracted with chloroform, dried over sodium carbonate and recrystallized from n-hexane. The crystal is collected by filtration, and crystallized from dichloromethane/n-hexane to give 1-(4-piperidinyl)-3,4-dihydrothiocarbostyril (4.1 g) as pale yellow powder, m.p. 94 - 97°C. Example 1 1-(4-Piperidinyl)-3,4-dihydrothiocarbostyril (1.1 g), 4-ethoxy-2-methoxybenzoic acid (1.05 g) and bisoxooxazodinylphosphinyl chloride (1.4 g) are dissolved in dichloromethane (30 ml) and thereto is added triethylamine (1.4 ml), and the mixture is stirred at room temperature overnight. Water is added to the reaction mixture, and the mixture is extracted with chloroform, dried over sodium carbonate, and purified by silica gel column chromatography (eluent; ethyl acetate : n-hexane = 1 : 1) to give 1-[1-(2-methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrothiocarbostyril (0.9 g) as pale yellow amorphous. 1 H-NMR (CDCl 3 ) δ ppm; 1.42 (3H, t, J=7.0 Hz), 1.79 - 2.17 (2H, m), 2.26 - 2.59 (2H, m), 2.63 - 3.36 (6H, m), 3.59 - 3.64 (1H, m), 3.76 - 3.92 (3H, m), 4.04 (2H, q, J=7.0 Hz), 4.88 - 5.05 (1H, m), 5.92 - 6.13 (1H, m), 6.44 - 6.58 (2H, m), 7.06 - 7.45 (5H, m) Using the suitable starting materials, the compounds of the following Table 1 are obtained in the same manner as in Example 1. Example 34 1-[1-{4-[5-(4-Trifluoroacetylamino-1-piperidinyl)pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (1.8 g) is dissolved in methanol (40 ml), and thereto is added potassium carbonate (0.8 g). The mixture is stirred at room temperature overnight. The reaction solution is concentrated and thereto is added water. The mixture is extracted with chloroform, dried over sodium carbonate, and purified by silica gel column chromatography (eluent; dichloromethane : methanol = 10 : 1) to give 1-[1-{4-[5-(4-amino-1-piperidinyl)pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (1 g) as colorless oil. 1 H-NMR (CDCl 3 ) δ ppm: 1.30 - 1.68 (6H, m), 1.69 - 2.12 (8H, m), 2.15 - 2.40 (4H, m), 2.48 - 3.12 (11H, m), 3.87 - 5.00 (3H, m), 3.98 (2H, t, J=6.4 Hz), 6.82 - 6.93 (2H, m), 6.97 - 7.31 (4H, m), 7.35 - 7.48 (2H, m) Example 35 1-[1-{4-[5-(4-Amino-1-piperidinyl)pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (0.6 g) and acetic anhydride (0.2 ml) are dissolved in dichloromethane (20 ml), and thereto are added triethylamine (0.56 ml) and 1,4-dimethylaminopyridine (20 mg), and the mixture is stirred at room temperature overnight. Water is added to the reaction mixture and the mixture is extracted with chloroform, dried over sodium carbonate, and purified by silica gel column chromatography (eluent; dichloromethane : methanol = 20 : 1) to give 1-[1-{4-[5-(4-acetylamino-1-piperidinyl)pentyloxy]benzoyl)-4-piperidinyl]-3,4-dihydrocarbostytril (310 mg) as colorless oil. 1 H-NMR (CDCl 3 ) δ ppm: 1.41 - 1.93 (12H, m), 1.97 (3H, s), 2.08 - 2.26 (2H, m), 2.38 - 3.29 (12H, m), 3.70 - 5.08 (4H, m), 3.99 (2H, t, J=6.3 Hz), 5.60 - 5.73 (1H, m), 6.83 - 6.92 (2H, m), 6.95 - 7.31 (4H, m), 7.37 - 7.46 (2H, m) Using the suitable starting materials, the compounds of the above Examples 1 and 14 are obtained in the same manner as in Example 35. Example 36 1-{1-[4-(6-Diethylamino-5-hydroxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.7 g) and methyl isocyanate (0.24 ml) are dissolved in acetonitril (20 ml), and thereto is added trifluroboran ethyl ether complex (0.35 ml) under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction mixture is concentrated and purified by silica gel column chromatography (eluent; dichloromethane : methanol = 20 : 1) to give 1-{1-[4-(6-diethylamino-5-methylaminocarbonyloxyhexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (314 mg) as colorless oil. 1 H-NMR (CDCl 3 ) δ ppm: 1.00 (6H, t, J=7.1 Hz), 1.45 - 1.97 (8H, m), 2.40 - 3.10 (18H, m), 3.90 - 5.03 (4H, m), 3.9 (2H, t, J=6.2 Hz), 6.82 - 6.95 (2H, m), 6.98 - 7.33 (4H, m) 7.46 - 7.50 (2H, m) Example 37 1-{1-[4-{5-[(N-Methyl-N-(2-hydroxyethyl)amino]pentyloxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.9 g) and ethylmalonyl chloride (0.28 ml) are dissolved in dichloroethane (10 ml), and thereto is added diisopropylethylamine (0.48 ml) under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction mixture is concentrated and purified by silica gel column chromatography (eluent; dichloromethane : methanol = 20 : 1 to give 1-{1-[4-{5-[(N-methyl-N-(2-ethoxycarbonylacetyloxyethyl)amino]pentyloxy}benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.28 g) as colorless oil. 1 H-NMR (CDCl 3 ) δ ppm: 1.28 (3H, t, J=7.1 Hz), 1.38 - 1.93 (8H, m), 2.28 (3H, s), 2.35 - 3.10 (12H, m), 3.39 (2H, s), 3.82 - 4.96 (3H, m), 3.98 (2H, t, J=6.4 Hz), 4.19 (2H, q, J=7.1 Hz), 4.25 (2H, t, J=6.5 Hz), 6.83 - 7.46 (8H, m) Example 38 1-{1-[4-(4-Oxiranylbutoxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (4.6 g) is dissolved in methanol (100 ml), and thereto is added allylamine (10 ml), and the mixture is stirred overnight. The reaction mixture is concentrated and purified by silica gel column chromatography (eluent; dichloromethane : methanol = 10 : 1) to give 1-{1-[4-(5-hydroxy-6-allylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (2.5 g) as colorless oil. 1 H-NMR (CDCl 3 ) δ ppm: 1.40 - 1.92 (8H, m), 2.43 - 3.12 (12H, m), 3.21 - 3.42 (2H, m), 3.61 - 3.76 (1H, m), 3.82 - 3.94 (3H, m), 3.99 (2H, t, J=6.3 Hz), 5.10 - 5.28 (2H, m), 5.80 - 6.01 (1H, m), 6.85 - 7.48 (8H, m) Using the suitable starting materials, the compound of the above Example 6 is obtained in the same manner as in Example 38. Example 39 1-{1-[4-(5-Bromopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (2 g) and 4-trifluoroacetylaminopiperidine (2 g) are dissolved in dimethylformamide (40 ml), and thereto is added potassium carbonate (2 g) and the mixture is stirred overnight. The reaction mixture is poured into water, and the mixture is extracted with toluene/ethyl acetate (1 : 1), dried over magnesium sulfate, and purified by silica gel column chromatography (eluent; dichloromethane : methanol = 50 : 1) to give 1-[1-{4-[5-(4-trifluoroacetylamino-1-piperidinyl)pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (2 g) as colorless oil. 1 H-NMR (CDCl 3 ) δ ppm: 1.37 - 1.63 (6H, m), 1.68 - 2.17 (8H, m), 2.30 - 2.41 (2H, m), 2.52 - 3.10 (10H, m), 3.70 - 5.04 (4H, m), 4.00 (2H, t, J=6.4 Hz), 6.35 - 6.50 (1H, m), 6.85 - 6.95 (2H, m), 6.98 - 7.31 (4H, m), 7.37 - 7.47 (2H, m) Using the suitable starting materials, the compounds of the above Examples 2 - 10 and 15 are obtained in the same manner as in Example 39. Example 40 To the mixture of conc. hydrochloric acid (3.2 ml) and ethanol (2 ml) is added 1-[1-{4-[2-(2-nitrophenyl)thio1-imidazolyl]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril (2.0 g), and thereto is added dropwise a solution of stannous chloride dihydrate (2.7 g) in ethanol (4 ml) at a temperature below 25°C with water-cooling, and the mixture is stirred at room temperature for two hours. The mixture is poured into ice-water and basified with aqueous sodium hydroxide solution, extracted with chloroform, washed with water, and dried over sodium sulfate. After concentrated under reduced pressure, the resulting residue is purified by silica gel column chromatography (eluent; chloroform : methanol = 50 : 1 - 25 : 1), and further dissolved in methanol. The mixture is added dropwise with stirring into water (about 40 ml) and the resulting precipitates are collected by filtration and dried to give 1-[1-{4-[2-(2-aminophenyl)thio-1-imidazolyl]benzoyl}-4-piperidinyl}-3,4-dihydrocarbostyril (1.6 g) as white powder. 1 H-NMR (CDCl 3 ) δ ppm: 1.7 - 2.1 (2H, m), 2.5 - 3.5 (10H, m), 3.7 - 4.2 (1H, m), 4.2 - 4.5 (1H, m), 4.6 - 5.2 (1H, m), 6.47 (1H, dt, J=1.2 Hz, J=8.0 Hz), 7.62 (1H, dd, J=1.2 Hz, J=8.0 Hz), 6.95 (1H, dd, J=1.2 Hz, J=8.0 Hz), 7.0 - 7.3 (7H, m), 7.34 (2H, d, J=8.4 Hz), 7.54 (2H, d, J=8.4 Hz) Example 41 To a solution of 1-{1-[4-(2-imidazolyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (1.0 g) and potassium carbonate (0.35 g) in dimethylformamide (10 ml) is added methyl iodide (0.16 ml) under ice-cooling, and the mixture is stirred at room temperature overnight. Further, to the mixture are added methyl iodide (0.16 ml) and potassium carbonate (0.3 g), and the mixture is stirred at room temperature for 8 hours. The mixture is poured into ice-water, extracted with ethyl acetate, washed with water and dried over sodium sulfate. After concentrated under reduced pressure, the resulting residue is purified by silica gel column chromatography (eluent; dichloromethane : methanol = 25 : 1) and recrystallized from ethyl acetate to give 1-{1-[4-(1-methyl-2-imidazolyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril (0.15 g) as colorless scales, m.p. 177 - 179°C. Pharmacological Test Experiment 1 : V 1 receptor binding assay Using rat liver plasma membrane preparations prepared according to Ichihara's method [cf: Akira Ichihara, J. Bio. Chem., 258 , 9283 (1983)], the plasma membrane (50000dpm, 2x10 -10 M) of [H] 3 -Arg-vasopressin and a test compound (100 ng, 10 -7 -10 -4 M) are incubated at 37°C for 10 minutes in 100 mM Tris-HCl buffer (pH: 8.0, 250 µl) containing 5 mM MgCl 2 , 1 mM MEDTA and 0.1 % BSA. After incubation, the mixture is filtered three times using the glass filter (GF/F) so as to separate the membrane preparation combined with vasopressin and then washed with the buffer (5 ml). This glass filter is taken out and mixed with liquid scintillation cocktail. The amount of [H] 3 -vasopressin combined with the membrane is measured by liquid scintillation counter and the rate of the inhibitory effect of the test compound is estimated according to the following equation. Rate of the inhibitory effect (%) = 100 - C 1 - B 1 C 0 - B 1 X 100 C 1 : The amount of [H] 3 -vasopressin combined with the membrane in the presence of the test compound (in prescribed amount). C 0 : The amount of [H] 3 -vasopressin combined with the membrane in the absence of the test compound. B 1 : The amount of [H] 3 -vasopressin combined with the membrane in the presence of the excess amount of vasopressin (10 -6 M). The results are expressed as IC 50 values, which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50 %. The results are shown in the following Table 2. Test compound 1. 1-[1-{4-[5-(Cyclohexanespiro-4'-(1-piperidinyl))pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 2. 1-{1-[4-(5-Tricyclo[3.3.1.1 3.7 ]decanylaminopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril hydrochloride 3. 1-{1-[4-(5-Tricyclo[3.3.1.1 3.7 ]decanylmethylaminopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril 4. 1-[1-{4-[5-(2,2,2-Trifluoroethylamino)pentyloxy)benzoyl}-4-piperidinyl}-3,4-dihydrocarbostyril 5. 1-[1-{4-[5-{N-Methyl-N-(2-ethoxycarbonylacetyloxyethyl)amino}pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 6. 1-{1-[4-(5-Hydroxy-6-allylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril 7. 1-[1-{4-[5-(4-Amino-1-piperidinyl)pentyloxy)benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 8. 1-[1-{4-[5-(4-Trifluoroacetylamino-1-piperidinyl)pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 9. 1-[1-{4-[5-(4-Acetylamino-1-piperidinyl)pentyloxy)benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 10. 1-{1-[4-(5-Methylaminocarbonyloxy-6-diethylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril 11. 1-[1-(2-Methoxy-4-ethoxybenzoyl)-4-piperidinyl]-3,4-dihydrothiocarbostyril 12. 1-[1-{4-[5-(1-Pyrrolidinyl)pentylthio]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 13. 1-{1-[4-(2-Pyridyl)benzoyl}-4-piperidinyl}3,4-dihydrocarbostyril 14. 1-{1-[4-(2-Imidazolyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril 15. 1-[1-{4-[2-(2-Aminophenylthio)-1-imidazolyl]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 16. 1-[1-(2-Methoxy-4-allylthiobenzoyl)-4-piperidinyl]-3,4-dihydrocarbostyril 17. 1-[1-{4-[5-(1-Pyrrolidinyl)pentylsulfinyl]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 18. 1-[1-{4-[5-(1-Pyrrolidinyl)pentylsulfonyl]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril 19. 1-{1-[4-(2-Benzimidazolyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril 20. 1-{1-[4-(2-Phenyl-1-imidazolyl)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril 21. 1-[1-{4-[2-(4-Methoxyphenyl)-1-imidazolyl]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril Test Co. No. IC 50 (µM) Test Co. No. IC 50 (µM) 1 0.047 2 0.027 3 0.10 4 0.32 5 0.11 6 0.14 7 0.028 8 0.063 9 0.036 10 0.038 11 0.73 12 0.034 13 1.2 14 1.4 15 0.80 16 0.11 17 3.0 18 1.9 19 2.1 20 2.8 21 2.7

Claims: Claims for the following Contracting States : CH, DE, DK, FR, GB, IT, LI, NL, SE A carbostyril derivative of the following formula: wherein X is oxygen or sulfur, Y is hydrogen or C 1-6 alkyl, R A is a group of the formula: wherein n is 1 or 2, A is C 1-6 alkylene, and R 1 is benzoyl which phenyl ring may optionally have one to three substituents selected from C 1-6 alkoxy and amino having optionally a C 1-6 alkyl substituent, or R A is a group of the formula: wherein n is as defined above, and R 2A is a group of the formula: {wherein R 3A is i) C 1-6 alkoxy, ii) a 5- or 6-membered heterocylic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substituent selected from nitro and amino, iii) C 2-6 alkenylthio, iv) pyrrolidinyl-substituted C 1-6 alkylthio, v) pyrrolidinyl-substituted C 1-6 alkylsulfinyl, vi) pyrrolidinyl-substituted C 1-6 alkylsulfonyl, vii) a group of the formula: [wherein B is C 1-6 alkylene having optionally a hydroxy substituent, R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 alkoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is amino which may optionally be substituted by C 1-6 alkanoyl having optionally one to three halogen substituents)], or viii) C 1-6 alkoxy having two substituents selected from aminocarbonyloxy having optionally a C 1-6 alkyl substituent and a group of the formula: (R 7 and R 8 are the same or different and are each hydrogen or C 1-6 alkyl), m is an integer of 1 to 3}, or R 2A is a group of the formula {wherein R 3B is a 7- to 10-membered monocyclic or dicyclic hetrocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substitutent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substitutent selected from nitro and amino}, the bond between 3- and 4-positions of the carbostyril ring is a single bond or a double bond, provided that when all of R 3A are C 1-6 alkoxy or when R 5 is C 1-6 alkanoyl, X is sulfur, and that when R 5 is C 2-6 alkenyl and X is oxygen, B is C 1-6 alkylene having a hydroxy substituent, and further that when R 3A is a heterocyclic group having C 1-6 alkyl or oxo substituent, the heterocyclic group is bound to the phenyl ring at a position other than the hetero atom, or a salt thereof. The compound according to claim 1, which is a compound of the formula: wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril ring are as defined in claim 1, R 3B is a 7- to 10-membered monocyclic or dicyclic hetrocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substitutent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substitutent selected from nitro and amino, or a salt thereof. The compound according to claim 1, wherein X is oxygen, and R is a group of the formula: wherein A, n and R 1 are as defined in claim 1, or a salt thereof. The compound according to claim 1, wherein X is oxygen, and R is a group of the formula: wherein n and R 2A are as defined in claim 1, or a salt thereof. The compound according to claim 1, wherein X is sulfur, and R is a group of the formula: wherein A, n and R 1 are as defined in claim 1, or a salt thereof. The compound according to claim 1, wherein X is sulfur, and R is a group of the formula: wherein n and R 2A are as defined in claim 1, or a salt thereof. The compound according to claim 2, wherein X is oxygen and the bond between 3- and 4-positions of the carbostyril nucleus is a single bond, or a salt thereof. The compound according to claim 2, wherein X is oxygen and the bond between 3- and 4-positions of the carbostyril nucleus is a double bond, or a salt thereof. The compound according to claim 2, wherein X is sulfur, or a salt thereof. The compound according to claim 4, wherein n is 1, or a salt thereof. The compound according to claim 4, wherein n is 2, or a salt thereof. The compound according to claim 7, wherein n is 1, and a salt thereof. The compound according to claim 7, wherein n is 2, or a salt thereof. The compound according to claim 11, wherein R 3A is i) C 1-6 alkoxy, ii) a 5- or 6-membered heterocylic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring, and a phenylthio having optionally a substituent selected from nitro and amino, iii) C 2-6 alkenylthio, or iv) C 1-6 alkoxy having two substituents selected from aminocarbonyloxy having optionally a C 1-6 alkyl substituent and a group of the formula: (R 7 and R 8 are as defined in claim 1), or a salt thereof. The compound according to claim 11, wherein R 3A is pyrrolidinyl-substituted C 1-6 alkylthio, pyrrolidinyl-substituted C 1-6 alkylsulfinyl, or pyrrolidinyl-substituted C 1-6 alkylsulfonyl, or a salt thereof. The compound according to claim 11, wherein R 3A is a group of the formula: [wherein B is C 1-6 alkylene having optionally a hydroxy substituent, R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 alkoxycarbonyl C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is an amino which may optionally be substituted by a lower alkanoyl having optionally one to three halogen substituents)], or a salt thereof. The compound according to claim 13, wherein Y is hydrogen, or a salt thereof. The compound according to claim 13, wherein Y is C 1-6 alkyl, or a salt thereof. The compound according to claim 16, wherein R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 alkoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or a salt thereof. The compound according to claim 16, wherein R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is as defined in claim 16), or a salt thereof. The compound according to any one of claim 14, 15, 19 or 20, wherein Y is hydrogen, and the bond between 3- and 4-positions of the carbostyril nucleus is a single bond, or a salt thereof. The compound according to any one of claim 14, 15, 19 or 20, wherein Y is C 1-6 alkyl and the bond between 3- and 4-positions of the carbostyril nucleus is a single bond, or a salt thereof. The compound according to any one of claim 14, 15, 19, or 20, wherein Y is hydrogen and the bond between 3- and 4-positions of the carbostyril nucleus is a double bond, and a salt thereof. The compound according to any one of claim 14, 15, 19, or 20, wherein Y is a C 1-6 alkyl and the bond between 3- and 4-positions of the carbostyril nucleus is a double bond, or a salt thereof. 1-{1-[4-[5-(4-Acetylamino-1-piperidinyl)pentyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. 1-{1-[4-(5-Tricyclo[3.3.1.1 3,7 ]decanylaminopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. 1-{1-[4-(5-Hydroxy-6-allylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. 1-{1-[4-[5-(4-Trifluoroacetylamino-1-piperidinyl)pentyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. 1-{1-[4-[5-(1-Pyrrolidinyl)pentylthio]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. A vasopressin antagonistic composition which comprises as an active ingredient a compound of the formula (1) as set forth in claim 1, or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier or diluent. A vasopressin antagonistic composition which comprises as an active ingredient a compound of the formula (1B) as set forth in claim 2, or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier or diluent. A process for preparing a compound of the formula (1) as set forth in claim 1, which comprises the following steps of (a) cyclizing a compound of the formula (2): wherein Y is as defined in claim 1, R is the same as R A as defined in claim 1 or a group of the formula: wherein n and R 3B are as defined in claim 1, and D is a group of the formula: -CH=CHR 14 (R 14 is C 1-6 alkoxy, phenyl or halogen), a group of the formula: (R 9 and R 10 are each C 1-6 alkyl), or a group of the formula: -C≡CH, to give a compound of the formula (1a): wherein Y is as defined in claim 1 and R is as defined above, (b) reducing a compound of the formula (1a) to give a compound of the formula (1b), or alternatively dehydrogenating a compound of the formula (1b) with an oxidizing agent to give a compound of the formula (1a) as shown in the following reaction scheme: wherein Y is as defined in claim 1, and R is as defined above, (c) cyclizing a compound of the formula (3): wherein Y is as defined in claim 1, and R is as defined above, to give a compound of the formula (1a) as shown hereinabove, (d) cyclizing a compound of the formula (4): wherein Y is as defined in claim 1 and R is as defined above, to give a compound of the formula (1c): wherein Y and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1 and R is as defined above, (e) reacting a compound of the formula (5): wherein X, Y and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, with a compound of the formula (6): RX 1 (wherein R is as defined above and X 1 is halogen) to give a compound of the formula (1), (f) reacting a compound of the formula (1d): wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, with a compound of the formula (7): R 2 OH (wherein R 2 is the same groups as R 2A as defined in claim 1), to give a compound of the formula (1e): wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1 and R 2 is as defined above, (g) reacting a compound of the formula (1d'): wherein X, Y, A, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, with a compound of the formula (7a): R 1 OH (wherein R 1 is as defined in claim 1) to give a compound of the formula (1e'): wherein R 1 , X, Y, A, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, (h) reacting a compound of the formula (1j): wherein X, Y, n, R 3A , B, and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, and X 1 is as defined above, and p and p' are each an integer of 1 to 3, provided that p + p' is not more than 3, with a compound of the formula (10): HNR 4 R 5 (wherein R 4 and R 5 are as defined in claim 1) to give a compound of the formula (1k): wherein X, Y, R 3A , n, R 4 , R 5 , B, and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, p is as defind above, and p" is an integer of 1 to 3, provided that p + p" is not more than 3, (i) cyclizing a compound of the formula (1ℓ): wherein Y is as defined in claim 1, and R and X 1 are as defined above, to give a compound of the formula (1b), (j) reacting a compound of the formula (12): wherein X, Y, R 3A , n, and the bond between 3- and 4-positions of the carbostyril nucleus are as in claim 1, and p and p" are as defined above, and R 3b is an oxilanyl-substituted C 1-6 alkoxy, with a compound of the formula (13): HNR 4 R 5 (R 4 and R 5 are as defined in claim 1) to give a compound of the formula (14): wherein X, Y, R 3A , n, and the bond between 3- and 4-positions of the carbostyril nucleus are as in claim 1, and R 3C is C 1-6 alkoxy having a substituent selected from a group of the formula: (R 4 and R 5 are the same as defined in claim 1) and hydroxy, and p"' is an integer of 1 to 3, provided that p + p"' is not more than 3, (k) cyclizing a compound of the formula (27): wherein Y is as defined in claim 1, R is as defined above, an R 17 is C 1-6 alkoxycarbonyl, to give a compound of the formula (1b), (ℓ) reacting a compound of the formula (1p) with a compound of the formula (39) or (40) to give a compound of the formula (1q), or alternatively subjecting the compound of the formula (1q) to hydrolysis to give the compound of the formula (1p) as shown in the following reaction scheme: wherein X, Y, R 3A , B, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1, p, p', p" are as defined above, and R 6a is amino, R 6b is amino substituted by C 1-6 alkanoyl having optionally 1 to 3 halogen substituents, and R 23 is C 1-6 alkanoyl having optionally 1 to 3 halogen substituents, (m) reacting a compound of the formula (1c) with phosphorus pentasulfide or Lawesson's reagent to give a compound of the formula (1t): wherein Y and the bond between 3- and 4-positions of the carbostyril nucleus are as defined in claim 1 and R is as defined above. 1-[1-{4-[5-{N-Methyl-N-(2-ethoxycarbonylacetyloxyethyl)amino}pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril. A vasopressin antagonistic composition which comprises as an active ingredient a compound of as set forth in claim 33, or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable carrier or diluent. Claims for the following Contracting State : ES A process for preparing a carbostyril derivative of the following formula: wherein X is oxygen or sulfur, Y is hydrogen or C 1-6 alkyl, R A is a group of the formula: wherein n is 1 or 2, A is C 1-6 alkylene, and R 1 is benzoyl which phenyl ring may optionally have one to three substituents selected from C 1-6 alkoxy and amino having optionally a C 1-6 alkyl substituent, or R A is a group of the formula: wherein n is as defined above, and R 2A is a group of the formula: {wherein R 3A is i) C 1-6 alkoxy, ii) a 5- or 6-membered neterocylic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substituent selected from nitro and amino, iii) C 2-6 alkenylthio, iv) pyrrolidinyl-substituted C 1-6 alkylthio, v) pyrrolidinyl-substituted C 1-6 alkylsulfinyl, vi) pyrrolidinyl-substituted C 1-6 alkylsulfonyl, vii) a group of the formula: [wherein B is C 1-6 alkylene having optionally a hydroxy substituent, R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 -alkyl, C 1-6 -alkoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is amino which may optionally be substituted by C 1-6 alkanoyl having optionally one to three halogen substituents)], or viii) C 1-6 alkoxy having two substituents selected from aminocarbonyloxy having optionally a C 1-6 alkyl substituent and a group of the formula: (R 7 and R 8 are the same or different and are each hydrogen or C 1-6 alkyl), m is an integer of 1 to 3}, or R 2A is a group of the formula {wherein R 3B is a 7- to 10-membered monocyclic or dicyclic hetrocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substitutent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substitutent selected from nitro and amino}, the bond between 3- and 4-positions of the carbostyril ring is a single bond or a double bond, provided that when all of R 3A are C 1-6 alkoxy or when R 5 is C 1-6 alkanoyl, X is sulfur, and that when R 5 is C 2-6 alkenyl and X is oxygen, B is C 1-6 alkylene having a hydroxy substituent, and further that when R 3A is a heterocyclic group having C 1-6 alkyl or oxo substituent, the heterocyclic group is bound to the phenyl ring at a position other than the hetero atom, or a salt thereof, which process comprises the following steps of (a) cyclizing a compound of the formula (2): wherein Y is as defined above, R is the same as R A as defined above or a group of the formula: wherein n and R 3B are as defined above, and D is a group of the formula: -CH=CHR 14 (R 14 is C 1-6 alkoxy, phenyl or halogen), a group of the formula: (R 9 and R 10 are each C 1-6 alkyl), or a group of the formula: -C≡CH, to give a compound of the formula (1a): wherein Y and R are as defined above, (b) reducing a compound of the formula (1a) to give a compound of the formula (1b), or alternatively dehydrogenating a compound of the formula (1b) with an oxidizing agent to give a compound of the formula (1a) as shown in the following reaction scheme: wherein Y and R are as defined above, (c) cyclizing a compound of the formula (3): wherein Y and R are as defined above, to give a compound of the formula (1a) as shown hereinabove, (d) cyclizing a compound of the formula (4): wherein Y and R are as defined above to give a compound of the formula (1c): wherein Y, the bond between 3- and 4-positions of the carbostyril nucleus and R are as defined above, (e) reacting a compound of the formula (5): wherein X, Y and the bond between 3- and 4-positions of the carbostyril nucleus are as defined above, with a compound of the formula (6): RX 1 (wherein R is as defined above and X 1 is halogen) to give a compound of the formula (1), (f) reacting a compound of the formula (1d): wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined above, with a compound of the formula (7): R 2 OH (wherein R 2 is the same groups as R 2A as defined above to give a compound of the formula (1e): wherein X, Y, n, the bond between 3- and 4-positions of the carbostyril nucleus and R 2 are as defined above, (g) reacting a compound of the formula (1d'): wherein X, Y, A, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined above, with a compound of the formula (7a): R 1 OH (wherein R 1 is as defined above) to give a compound of the formula (1e'): wherein R 1 , X, Y, A, n and the bond between 3- and 4-positions of the carbostyril nucleus are as defined above, (h) reacting a compound of the formula (1j): wherein X, Y, n, R 3A , B, the bond between 3- and 4-positions of the carbostyril nucleus and X 1 are as defined above, and p and p' are each an integer of 1 to 3, provided that p + p' is not more than 3, with a compound of the formula (10): HNR 4 R 5 (wherein R 4 and R 5 are as defined above) to give a compound of the formula (1k): wherein X, Y, R 3A , n, R 4 , R 5 , B, the bond between 3- and 4-positions of the carbostyril nucleus and p are as defind above, and p" is an integer of 1 to 3, provided that p + p" is not more than 3, (i) cyclizing a compound of the formula (1ℓ): wherein Y, R and X 1 are as defined above, to give a compound of the formula (1b), (j) reacting a compound of the formula (12): wherein X, Y, R 3A , n, the bond between 3- and 4-positions of the carbostyril nucleus, and p and p" are as defined above, and R 3b is an oxilanyl-substituted C 1-6 alkoxy, with a compound of the formula (13): HNR 4 R 5 (R 4 and R 5 are as defined above) to give a compound of the formula (14): wherein X, Y, R 3A , n, and the bond between 3- and 4-positions of the carbostyril nucleus are as defined above, and R 3c is C 1-6 alkoxy having a substituent selected from a group of the formula: (R 4 and R 5 are the same as defined above) and hydroxy, and p"' is an integer of 1 to 3, provided that p + p"' is not more than 3, (k) cyclizing a compound of the formula (27): wherein Y and R are as defined above, and R 17 is C 1-6 alkoxycarbonyl, to give a compound of the formula (1b), (ℓ) reacting a compound of the formula (1p) with a compound of the formula (39) or (40) to give a compound of the formula (1q), or alternatively subjecting the compound of the formula (1q) to hydrolysis to give the compound of the formula (1p) as shown in the following reaction scheme: wherein X, Y, R 3A , B, n, the bond between 3- and 4-positions of the carbostyril nucleus, p, p', and p" are as defined above, and R 6a is amino, R 6b is amino substituted by C 1-6 alkanoyl having optionally 1 to 3 halogen substituents, and R 23 is C 1-6 alkanoyl having optionally 1 to 3 halogen substituents, (m) reacting a compound of the formula (1c) with phosphorus pentasulfide or Lawesson's reagent to give a compound of the formula (1t): wherein Y, the bond between 3- and 4-positions of the carbostyril nucleus and R are as defined above. The process according to claim 1, wherein the prepared compound is having the formula: wherein X, Y, n and the bond between 3- and 4-positions of the carbostyril ring are as defined in claim 1, R 3B is a 7- to 10-membered monocyclic or dicyclic hetrocyclic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substitutent selected from halogen and C 1-6 alkoxy on the phenyl ring, and phenylthio having optionally a substitutent selected from nitro and amino, or a salt thereof. The process according to claim 1, wherein X is oxygen, and R is a group of the formula: wherein A, n and R 1 are as defined in claim 1, or a salt thereof. The process according to claim 1, wherein X is oxygen, and R is a group of the formula: wherein n and R 2A are as defined in claim 1, or a salt thereof. The process according to claim 1, wherein X is sulfur, and R is a group of the formula: wherein A, n and R 1 are as defined in claim 1, or a salt thereof. The process according to claim 1, wherein X is sulfur, and R is a group of the formula: wherein n and R 2A are as defined in claim 1, or a salt thereof. The process according to claim 2, wherein X is oxygen and the bond between 3- and 4-positions of the carbostyril nucleus is a single bond, or a salt thereof. The process according to claim 2, wherein X is oxygen and the bond between 3- and 4-positions of the carbostyril nucleus is a double bond, or a salt thereof. The process according to claim 2, wherein X is sulfur, or a salt thereof. The process according to claim 4, wherein n is 1, or a salt thereof. The process according to claim 4, wherein n is 2, or a salt thereof. The process according to claim 7, wherein n is 1, and a salt thereof. The process according to claim 7, wherein n is 2, or a salt thereof. The process according to claim 11, wherein R 3A is i) C 1-6 alkoxy, ii) a 5- or 6-membered heterocylic group having 1 to 2 hetero atoms selected from nitrogen, oxygen and/or sulfur which may optionally have a substitutent selected from C 1-6 alkyl, oxo, phenyl having optionally a substituent selected from halogen and C 1-6 alkoxy on the phenyl ring, and a phenylthio having optionally a substituent selected from nitro and amino, iii) C 2-6 alkenylthio, or iv) C 1-6 alkoxy having two substituents selected from aminocarbonyloxy having optionally a C 1-6 alkyl substituent and a group of the formula: (R 7 and R 8 are as defined in claim 1), or a salt thereof. The process according to claim 11, wherein R 3A is pyrrolidinyl-substituted C 1-6 alkylthio, pyrrolidinyl-substituted C 1-6 alkylsulfinyl, or pyrrolidinyl-substituted C 1-6 alkylsulfonyl, or a salt thereof. The process according to claim 11, wherein R 3A is a group of the formula: [wherein B is C 1-6 alkylene having optionally a hydroxy substituent, R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 alkoxycarbonyl C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is an amino which may optionally be substituted by a lower alkanoyl having optionally one to three halogen substituents)], or a salt thereof. The process according to claim 13, wherein Y is hydrogen, or a salt thereof. The process according to claim 13, wherein Y is C 1-6 alkyl, or a salt thereof. The process according to claim 16, wherein R 4 is hydrogen and R 5 is tricyclo[3.3.1.1]decanyl, tricyclo[3.3.1.1]decanyl-C 1-6 alkyl, halogen-substituted C 1-6 alkyl, C 1-6 alkoxycarbonyl-C 2-6 alkanoyloxy-C 1-6 alkyl, C 1-6 alkanoyl, or C 2-6 alkenyl, or a salt thereof. The process according to claim 16, wherein R 4 and R 5 may bind together with the nitrogen atom to which they bond to form a group of the formula: (R 6 is as defined in claim 16), or a salt thereof. The process according to any one of claim 14, 15, 19 or 20, wherein Y is hydrogen, and the bond between 3- and 4-positions of the carbostyril nucleus is a single bond, or a salt thereof. The process according to any one of claim 14, 15, 19 or 20, wherein Y is C 1-6 alkyl and the bond between 3- and 4-positions of the carbostyril nucleus is a single bond, or a salt thereof. The process according to any one of claim 14, 15, 19, or 20, wherein Y is hydrogen and the bond between 3- and 4-positions of the carbostyril nucleus is a double bond, and a salt thereof. The process according to any one of claim 14, 15, 19, or 20, wherein Y is a C 1-6 alkyl and the bond between 3- and 4-positions of the carbostyril nucleus is a double bond, or a salt thereof. The process according to claim 1 wherein the prepared compound is 1-{1-[4-[5-(4-Acetylamino-1-piperidinyl)pentyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. The process according to claim 1 wherein the prepared compound is 1-{1-[4-(5-Tricyclo[3.3.1.1 3,7 ]decanylaminopentyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. The process according to claim 1 wherein the prepared compound is 1-{1-[4-(5-Hydroxy-6-allylaminohexyloxy)benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. The process according to claim 1 wherein the prepared compound is 1-{1-[4-[5-(4-Trifluoroacetylamino-1-piperidinyl)pentyloxy]benzoyl]-4-piperidinyl}-3,4-dihydrocarbostyril. The process according to claim 1 wherein the prepared compound is 1-{1-[4-[5-(1-Pyrrolidinyl)pentylthio]benzoyl]4-piperidinyl}-3,4-dihydrocarbostyril. A process for preparing a vasopressin antagonistic composition which comprises admixing as an active ingredient a compound of the formula (1) as set forth in claim 1, or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier or diluent. A process for preparing a vasopressin antagonistic composition which comprises admixing as an active ingredient a compound of the formula (1B) as set forth in claim 2, or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier or diluent. The process according to claim 1 wherein the prepared compound is 1-[1-{4-[5-{N-Methyl-N-(2-ethoxycarbonylacetyloxyethyl)amino}pentyloxy]benzoyl}-4-piperidinyl]-3,4-dihydrocarbostyril. A process for preparing a vasopressin antagonistic composition which comprises admixing as an active ingredient a compound of as set forth in claim 32, or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable carrier or diluent.

Inventors: FUJIOKA TAKAFUMI, KITANO KAZUYOSHI E OTSUKA-IMAG, KOMATSU HAJIME, KONDO KAZUMI, MIYAMOTO HISASHI, NAKAYA KENJI, OGAWA HIDENORI, TANAKA MICHINORI, TERAMOTO SHUJI, TOMINAGA MICHIAKI, YABUUCHI YOICHI, YAMASHITA HIROSHI, FUJIOKA, TAKAFUMI, KITANO, KAZUYOSHI, KOMATSU, HAJIME, KONDO, KAZUMI, MIYAMOTO, HISASHI, NAKAYA, KENJI, OGAWA, HIDENORI, TANAKA, MICHINORI, TERAMOTO, SHUJI, TOMINAGA, MICHIAKI, YABUUCHI, YOICHI, YAMASHITA, HIROSHI, KITANO, KAZUYOSHI, E213, OTSUKA-IMAGIRE-RYO
Applicants: OTSUKA PHARMA CO LTD, OTSUKA PHARMACEUTICAL CO., LTD.
Application year: 1991
Main classification: C07D401
IPC codes: C07D401, A61P9, A61K31, A61P3, A61P5, A61P15, A61P13, C07D215, A61P1, A61P7