Carbostyril derivatives and salts thereof, processes for preparing the same and cardiotonic composition containing the same

Claim 2

Carbostyril derivative and salt thereof represented by the general formula (1), wherein R is an alkenyl group having 7 -12 carbon atoms, a phenyl-lower alkenyl group which may have, on the phenyl ring, lower alkylthio groups or lower alkylsulfinyl groups as the substituents, a phenyl-lower alkynyl group, a phenyl group which may have 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring, or a group of the formula (wherein A is a lower alkylene group; R' is a hydrogen atom, a lower alkyl group or a phenyl group; and R 2 is a phenyl group which may have 1 to 3 substituents selected from the group consisting of a hydroxy group, a-halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkanoylamino group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring); the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton is a single or double bond.

Claim 3

The carbostyril derivative and salt thereof according to Claim 1, wherein R is a group of the formula (wherein R' and R 2 are the same as defined in claim 1).

Claim 4

The carbostyril derivative and salt thereof according to Claim 1, wherein R is an alkenyl group having 7 to 12 carbon atoms.

Claim 5

The carbostyril derivative and salt thereof according to Claim 1, wherein R is a phenyl-lower alkenyl group which may have, on the phenyl ring, lower alkylthio groups or lower alkylsulfinyl groups as the substituents.

Claim 6

The carbostyril derivative and salt thereof according to Claim 1, wherein R is a phenyl group which may have 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group and a lower alkylsulfinyl group on the phenyl ring.

Claim 7

The carbostyril derivative and salt thereof according to Claim 2, wherein R' is a hydrogen atom.

Claim 8

The carbostyril derivative and salt thereof according to Claim 2, wherein R' is a lower alkyl group or a phenyl group.

Claim 9

The carbostyril derivative and salt thereof according to Claim 6, wherein the substituted position of a side-chain of the formula (wherein R is the same as defined above) is 6- position in the carbostyril skeleton.

Claim 10

The carbostyril derivative and salt thereof according to Claim 7, wherein the substituted position of a side chain of the formula (wherein R is the same as defined above) is 6- position in the carbostyril skeleton.

Claim 11

The carbostyril derivative and salt thereof according to Claim 3, wherein the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton is a single bond.

Claim 12

6-[4-(2-Hydroxy-2-phenylethyl)-1-piperazinylcarbonyl]-3,4-dihydrocarobstyril

Claim 13

6-[4-(2-Hydroxy-2-phenylethyl)-1-piperazinylcarbonyl]-3,4-dihydrocarobstyril

Claim 14

6-{4-[2-Hydroxy-2-(3-chlorophenyl)ethyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 15

6-{4-[2-Hydroxy-2-(3-chlorophenyl)ethyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 16

6-{4-[3-Hydroxy-3-(4-methylphenyl)propyl]-1-piperazinylcarbonyl}carbostyril

Claim 17

6-{4-[3-Hydroxy-3-(4-methylphenyl)propyl]-1-piperazinylcarbonyl}carbostyril

Claim 18

6-{4-[3-Hydroxy-3-(4-methoxyphenyl)propyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 19

6-{4-[3-Hydroxy-3-(4-methoxyphenyl)propyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 20

6-{4-[3-Hydroxy-3-(4-methylphenyl)propyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 21

6-{4-[3-Hydroxy-3-(4-methylphenyl)propyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 22

6-{4-[3-Hydroxy-3-(4-methylthiophenyl)propyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 23

6-{4-[3-Hydroxy-3-(4-methylthiophenyl)propyl]-1-piperazinylcarbonyl}-3,4-dihydrocarbostyril

Claim 24

6-(4-Geranyl-1-piperazinylcarbonyl)-3,4-dihydrocarbostyril

Claim 25

6-(4-Geranyl-1-piperazinylcarbonyl)-3,4-dihydrocarbostyril

Claim 26

A process for preparing a carbostyril derivative and salt thereof represented by the general formula (1 wherein R and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, (a) by reacting a carbostyril derivative represented by the general formula (2), wherein the carbon-carbon bond between 3-and 4- position in the carbostyril skeleton is the same as defined above, with a piperazine derivative represented by the general formula (3), wherein R is the same as defined above; (b) by reacting a piperazinylcarbonyl carbostyril derivative represented by the general formula (4), wherein the carbon-carbon bond between 3-and 4- positions in the carbostyril skeleton is the same as defined above, with a compound represented by the general formula (5), wherein R is the same as defined above; and X' is a halogen atom, a lower alkanesulfonyloxy group, an arylsulfonyloxy group or an aralkylsulfonyloxy group; or (c) by reacting a carbostyril derivative represented by the general formula (7), wherein X is a hydroxy group, a halogen atom, a lower alkanesulfonyloxy group, an arylsulfonyloxy group or an aralkylsulfonyloxy group, and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, with a compound represented by the general formula (8), wherein R is the same as defined above; (d) by reacting a morpholinocarbonyl carbostyril derivative represented by the general formula (10), wherein the carbon-carbon bond between 3-and 4- positions are the same as defined above, with a compound represented by the formula (8), wherein R is the same as defined above.

Claim 27

A process for preparing a carbostyril derivative and salt thereof represented by the general formula (1 wherein R and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, (a) by reacting a carbostyril derivative represented by the general formula (2), wherein the carbon-carbon bond between 3-and 4- position in the carbostyril skeleton is the same as defined above, with a piperazine derivative represented by the general formula (3), wherein R is the same as defined above; (b) by reacting a piperazinylcarbonyl carbostyril derivative represented by the general formula (4), wherein the carbon-carbon bond between 3-and 4- positions in the carbostyril skeleton is the same as defined above, with a compound represented by the general formula (5), wherein R is the same as defined above; and X' is a halogen atom, a lower alkanesulfonyloxy group, an arylsulfonyloxy group or an aralkylsulfonyloxy group; or (c) by reacting a carbostyril derivative represented by the general formula (7), wherein X is a hydroxy group, a halogen atom, a lower alkanesulfonyloxy group, an arylsulfonyloxy group or an aralkylsulfonyloxy group, and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, with a compound represented by the general formula (8), wherein R is the same as defined above; (d) by reacting a morpholinocarbonyl carbostyril derivative represented by the general formula (10), wherein the carbon-carbon bond between 3-and 4- positions are the same as defined above, with a compound represented by the formula (8), wherein R is the same as defined above.

Claim 28

A process for preparing a carbostyril derivative and a salt thereof represented by the general formula (1-a), wherein A, R and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, by reducing a carbostyril derivative represented by the general formula (1-b), wherein A, R 2 and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above.

Claim 29

A process for preparing a carbostyril derivative and a salt thereof represented by the general formula (1-a), wherein A, R and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, by reducing a carbostyril derivative represented by the general formula (1-b), wherein A, R 2 and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above.

Claim 30

A process for preparing a carbostyril derivative and a salt thereof represented by the general formula (1-c), wherein R 3 and R 4 are the same or different from each other and are each a hydrogen atom or a lower alkyl group, and R', R 2 and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, by reacting a piperazinyl carbostyril derivative represented by the general formula (4), wherein the carbon-carbon bond between 3-and 4- positions in the carbostyril skeleton are the same as defined above, with a compound represented by the general formula (11), wherein R', R 2 , R 3 and R 4 are the same as defined above.

Claim 31

A process for preparing a carbostyril derivative and a salt thereof represented by the general formula (1-c), wherein R 3 and R 4 are the same or different from each other and are each a hydrogen atom or a lower alkyl group, and R', R 2 and the carbon-carbon bond between 3-and 4-positions in the carbostyril skeleton are the same as defined above, by reacting a piperazinyl carbostyril derivative represented by the general formula (4), wherein the carbon-carbon bond between 3-and 4- positions in the carbostyril skeleton are the same as defined above, with a compound represented by the general formula (11), wherein R', R 2 , R 3 and R 4 are the same as defined above.

Claim 32

A cardiotonic composition containing, as the active ingredient, a carbostyril derivative or salt thereof represented by the general formula (1) as claimed in Claim 1.