Cardiotonics

Claim 2

A cardiotonic agent comprising a carbostyril derivative of the formula: wherein R 1 is hydrogen atom or cyano group, and R 2 and R 3 are the same or different and are each hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl(lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), or a pharmaceutically acceptable salt thereof.-

Claim 3

The agent according, to claim 1, wherein R 1 in the active compound of the formula (I) is hydrogen atom.

Claim 4

The agent according to claim 1, wherein R 1 in the active compound of the formula (I) is cyano group.

Claim 5

The agent according to claim 2, wherein R 2 and R 3 in the active compound of the formula (I) in claim 1 are the same or different and are each hydrogen atom, a C 1 -C 6 alkyl group being optionally substituted by hydroxy group, a C 2 -C 6 alkenyl group, a phenyl group, a phenyl(C 1 -C 6 )alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a C 1 -C 6 alkoxy(C 1 -C 6 )alkoxy group, a halogen atom, a C 1 -C 6 alkoxy group, a nitro group, a C 1 -C 6 alkyl group, a cyano group, a C 1 -C 6 alkylthio group and a C 1 -C 6 alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, or a phenylsulfinyl(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring.

Claim 6

The agent according to claim 2, wherein R2 and R 3 in the active compound of the formula (I) in claim 1 are the same or different and are each a C 3 -C 8 cycloalkyl group, a phenylsulfonyl(C 1 -C 6 )alkyl group having optionally 1 to 3 C 1 -C 6 alkoxy substituents on the phenyl ring, a phenylthio(C 1 -C 6 )alkyl group, a phenoxy(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, a pyridyl(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the pyridine ring, a thienyl(C 1 -C 6 )alkyl group, a benzoyl(C 1 -C 6 )alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(C 2 -C 6 )alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a C 1 -C 6 alkyl group cr a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, and A is a C 1 -C 6 alkylene group which may optionally be interrupted with oxo group).

Claim 7

The agent according to claim 2, wherein R 2 in the active compound of the formula (I) in claim 1 is hydrogen atom, a C 1 -C 6 alkyl group being optionally substituted by hydroxy group, a C 2 -C 6 alkenyl group, a phenyl group, or a phenyl(C 1 -C 6 )alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a C 1 -C 6 alkoxy(C 1 -C 6 )alkoxy group', a halogen atom, a C 1 -C 6 alkoxy group, a nitro group, a C 1 -C 6 alkyl' group, a cyano group, a C 1 -C 6 alkylthio group and a C l -C 6 alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety; and R 3 in the formula (I) is a phenylsulfonyl(C 1 -C 6 )alkyl group having optionally 1 to 3 C 1 -C 6 alkoxy substituents on the phenyl ring, a phenylthio(C 1 -C 6 )alkyl group, a phenoxy(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, a pyridyl(C 1 -C 6 )-alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the pyridine ring, a thienyl(C 1 -C 6 )alkyl group, a benzoyl(C 1 -C 6 )alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(C 1 -C 6 )alkenyl group, or a group of the formula: (wherein R4 and R 5 are the same or different and are each a C 1 -C 6 alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, and A is a C 1 -C 6 alkylene group which may optionally be interrupted with oxo group), or a pharmaceutically acceptable salt thereof.

Claim 8

The agent according to claim 4, wherein R 2 is hydrogen atom, a C 1 -C 6 alkyl group being optionally substituted by hydroxy group, a C 2 -C 6 alkenyl group, a phenyl group, or a phenyl(C 1 -C 6 )alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a C 1 -C G alkoxy(C 1 -C 6 )alkoxy group, a halogen atom, a C 1 -C 6 alkoxy group, a nitro group, a C 1 -C 6 alkyl group, a cyano group, a C 1 -C 6 alkylthio group and a C 1 -C 6 alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, and R 3 is a phenyl(C 1 -C 6 )alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a C 1 -C 6 alkoxy(C 1 -C 6 )alkoxy group, a halogen atom, a C 1 -C 6 alkoxy group, a nitro group, a C 1 -C 6 alkyl group, a cyano group, a C 1 -C 6 alkylthio group and a C 1 -C 6 alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, or a phenylsulfinyl(C1-C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring.

Claim 9

The agent according to claim 7, wherein R 2 is hydrogen atom or a C 1 -C 6 alkyl group being optionally substituted by hydroxy group, and R 3 is a phenyl(C 1 -C 6 )alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a C 1 -C 6 alkoxy group and a halogen atom.

Claim 10

The agent according to claim 7, wherein R 2 is hydrogen atom or a C 1 -C 6 alkyl group being optionally substituted by hydroxy group, and R 3 is a phenylsulfinyl(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring.

Claim 11

The agent according to claim 1, wherein the active compound is selected from 6-[3-(3-methoxyben- zylamino)2-hydroxypropoxy]carbostyril, 6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]carbostyril; 6-[3-[N-methyl-N-(2-phenylsulfinylethyl)amino]-2-hydroxypropoxy]carbostyril; 6-[3-[N-(2-hydroxyethyl)-N-(4-fluorobenzyl)amino]-2-hydroxypropoxy]carbostyril; 6-[3-(3,4-diethoxybenzylamino)-2-hydroxypropoxy]carbostyril; 6-[3-(4-fluorobenzylamino)-2-hydroxypropoxy]carbostyril, and 6-[3-(3-ethoxybenzylamino)-2-hydroxypropoxy]carbostyril.

Claim 12

11: A carbostyril compound of the formula: wherein R 2 ' is hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl(lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), and R 3 ' is a phenyl(lower)alkyl group which has a hydroxy substituent on the alkyl moiety, a phenylsulfonyl-(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)-alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having 1 to 3 substituents of a halogen atom on the' phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 , R 5 and A are the same as defined above), or a pharmaceutically acceptable salt thereof.

Claim 13

11: A carbostyril compound of the formula: wherein R 2 ' is hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl(lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), and R 3 ' is a phenyl(lower)alkyl group which has a hydroxy substituent on the alkyl moiety, a phenylsulfonyl-(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)-alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having 1 to 3 substituents of a halogen atom on the' phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 , R 5 and A are the same as defined above), or a pharmaceutically acceptable salt thereof.

Claim 14

A carbostyril compound of the formula: wherein R2 is a lower alkyl group having a hydroxy substituent, and R 3 ' is a phenyl(lower)alkyl group having 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group, or a pharmaceutically acceptable salt thereof.

Claim 15

A carbostyril compound of the formula: wherein R2 is a lower alkyl group having a hydroxy substituent, and R 3 ' is a phenyl(lower)alkyl group having 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group, or a pharmaceutically acceptable salt thereof.

Claim 16

A carbostyril compound of the formula: wherein R 1' is cyano group, and R 2 and R 3 are the same or different and are each hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl (lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)-alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), or a pharmaceutically acceptable salt thereof.

Claim 17

A carbostyril compound of the formula: wherein R 1' is cyano group, and R 2 and R 3 are the same or different and are each hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl (lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)-alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), or a pharmaceutically acceptable salt thereof.

Claim 18

The compound according to claim 11, wherein R 2' is hydrogen atom or a C 1 -C6 alkyl group being optionally substituted by hydroxy group, a C 2 -C 6 alkenyl group, a phenyl group, or a phenyl(C 1 -C 6 )alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a C 1 -C 6 alkoxy(C 1 -C 6 )-alkoxy group, a halogen atom, a C 1 -C 6 alkoxy group, a nitro group, a C 1 -C 6 alkyl group, a cyano group, a C 1 -C 6 alkylthio group and a C 1 -C 6 alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, or a pharmaceutically acceptable salt thereof.

Claim 19

The compound according to claim 11 wherein R 2' is a C 3 -C 8 cycloalkyl group, a phenylsulfonyl(C 1 -C 6 )alkyl group having optionally 1 to C 1 -C 6 alkoxy substituents on the phenyl ring, a phenylthio(C 1 -C 6 )-alkyl group, a phenylsulfinyl(C l -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, a phenoxy(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, a pyridyl(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the pyridine ring, a thienyl(C 1 -C 6 )alkyl group, a benzoyl(C 1 -C 6 )alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(C 2 -C 6 )alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a Ci-C6 alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, and A is a C 1 -C 6 alkylene group which may optionally be interrupted with oxo group), or a pharmaceutically acceptable salt thereof.

Claim 20

The compound according to claim 12, wherein R 3 ' is a phenyl(C 1 -C 6 )alkyl group which has 1 to 3 substituents of a halogen atom, or a pharmaceutically acceptable salt thereof.

Claim 21

The compound according to claim 14, wherein R3 is a phenylsulfinyl(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, or a pharmaceutically acceptable salt thereof.

Claim 22

The compound according to claim 14, wherein R 3' is a phenyl(C 1 -C 6 )alkyl group having a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(C 1 -C 6 )alkyl group having optionally 1 to 3 C 1 -C 6 alkoxy substituents on the phenyl ring, a phenylthio(C 1 -C 6 )alkyl group, a phenoxy(C 1 -C 6 )alkyl group having 1 to 3 substituents of a halogen atom on the phenyl ring, a pyridyl(C,-C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the pyridine ring, a thienyl(C 1 -C 6 )alkyl group, a benzoyl(C 1 -C 6 )alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(C 2 -C 6 )alkenyl group, or a group of the formula: (wherein R4 and R 5 are the same or different and are each a C 1 -C 6 alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, and A is a C 1 -C 6 alkylene group which may optionally be interrupted with oxo group), or a pharmaceutically acceptable salt thereof.

Claim 23

The compound according to claim 15, wherein R 3 ' is a phenylsulfinyl(C 1 -C 6 )alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, or a pharmaceutical acceptable salt thereof.

Claim 24

The compound according to claim 17, wherein R 2 ' is hydrogen atom or a C 1 -C 6 alkyl group being optionally substituted by hydroxy group, and R 3 ' is a phenylsulfinyl(C 1 -C 6 )alkyl group having optionally 1 to 3 subsstituents selected from the group consisting of a halogen atom and a C 1 -C 6 alkoxy group on the phenyl ring, or a pharmaceutically acceptable salt thereof.

Claim 25

A pharmaceutical composition for the prophylaxis or treatment of heart diseases which comprises an effective amount of a carbostyril derivative as set forth in anyone of claims 11 to 20 in admixture with a pharmaceutically acceptable carrier or diluent.

Claim 26

The composition according to claim 21 wherein the active compound is selected from 6-[3-[N-(2-hydroxyethyl)-N-(4-fluorobenzyl)amino]-2-hydroxypropoxy]carbostyril and 6 -[ 3-[N-methyl-N-(2 - phenylsulfinylethyl)amino]-2-hydroxypropoxy]carbostyril.

Claim 27

A process for preparing a carbostyril derivative of the formula: wherein R 1 is hydrogen atom or cyano group, and R 2 and R 3 are the same or different and are each hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl(lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), and a pharmaceutically acceptable salt thereof, which comprises (a) reacting a compound of the formula: wherein R 1 is as defined above, and X is a halogen atom, a lower alkanesulfonyloxy group, an arylsulfonyloxy group, or an aralkylsulfonyloxy group, with a compound of the formula: wherein R 2 and R 3 are as defined above to give the compound of the formula (I), (b) reacting a compound of the formula: wherein R 1 is as defined above, and Y is the group of the formula: with a compound of the formula: wherein R 2 and R 3 are the same as defined above to give the compound of the formula (I), (c) reacting a compound of the formula: wherein R 1 is as defined above, with a compound of the formula: wherein R 2 , R 3 and X are as defined above to give a compound of the formula (I), (d) reacting a compound of the formula: wherein R 1 is as defined above, and R 6 is the same as R 2 as defined above except that benzoyl and anilinothiocarbonyl groups are excluded, with a compound of the formula: R 7 X (wherein X is as defined above and R 7 is the same as R 3 as defined above except that benzoyl and anilinothiocarbonyl groups are excluded to give a compound of the formula: wherein R 1 , R 6 and R 7 are as defined above, (e) reacting a compound of the formula: wherein R 1 and R 6 are as defined above, with a compound of the formula: R 8 X 1 wherein R 8 is benzoyl group and X 1 is hydroxy group to give a compound of the formula: wherein R 1 , R 6 and R 8 are as defined above, or (f) reacting a compound of the formula: wherein R 1 and R 6 are as defined above, with a compound of the formula: to give a compound of the formula: wherein R 1 and R 6 are as defined above.

Claim 28

A process for preparing a carbostyril derivative of the formula: wherein R 1 is hydrogen atom or cyano group, and R 2 and R 3 are the same or different and are each hydrogen atom, a lower alkyl group being optionally substituted by hydroxy group, a cycloalkyl group, a lower alkenyl group, a phenyl group, a phenyl(lower)alkyl group which has optionally 1 to 3 substituents selected from the group consisting of a lower alkoxy(lower)alkoxy group, a halogen atom, a lower alkoxy group, a nitro group, a lower alkyl group, a cyano group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring and further has optionally a hydroxy substituent on the alkyl moiety, a phenylsulfonyl(lower)alkyl group having optionally 1 to 3 lower alkoxy substituents on the phenyl ring, a phenylthio(lower)alkyl group, a phenylsulfinyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a phenoxy(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, a pyridyl(lower)alkyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the pyridine ring, a thienyl(lower)alkyl group, a benzoyl(lower)alkyl group, an anilinothiocarbonyl group, a benzoyl group, a pyridyl group, a phenyl(lower)alkenyl group, or a group of the formula: (wherein R 4 and R 5 are the same or different and are each a lower alkyl group or a phenyl group having optionally 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkoxy group on the phenyl ring, and A is a lower alkylene group which may optionally be interrupted with oxo group), and a pharmaceutically acceptable salt thereof, which comprises (a) reacting a compound of the formula: wherein R 1 is as defined above, and X is a halogen atom, a lower alkanesulfonyloxy group, an arylsulfonyloxy group, or an aralkylsulfonyloxy group, with a compound of the formula: wherein R 2 and R 3 are as defined above to give the compound of the formula (I), (b) reacting a compound of the formula: wherein R 1 is as defined above, and Y is the group of the formula: with a compound of the formula: wherein R 2 and R 3 are the same as defined above to give the compound of the formula (I), (c) reacting a compound of the formula: wherein R 1 is as defined above, with a compound of the formula: wherein R 2 , R 3 and X are as defined above to give a compound of the formula (I), (d) reacting a compound of the formula: wherein R 1 is as defined above, and R 6 is the same as R 2 as defined above except that benzoyl and anilinothiocarbonyl groups are excluded, with a compound of the formula: R 7 X (wherein X is as defined above and R 7 is the same as R 3 as defined above except that benzoyl and anilinothiocarbonyl groups are excluded to give a compound of the formula: wherein R 1 , R 6 and R 7 are as defined above, (e) reacting a compound of the formula: wherein R 1 and R 6 are as defined above, with a compound of the formula: R 8 X 1 wherein R 8 is benzoyl group and X 1 is hydroxy group to give a compound of the formula: wherein R 1 , R 6 and R 8 are as defined above, or (f) reacting a compound of the formula: wherein R 1 and R 6 are as defined above, with a compound of the formula: to give a compound of the formula: wherein R 1 and R 6 are as defined above.