Carbostyril compounds, compositions containing same and processes for preparing same

• US 4,760,064 A
• Filed: 12/13/1985
• Issued: 07/26/1988
• Est. Priority Date: 12/18/1984
• Status: Expired due to Fees

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: Tominaga, Michiaki, Nakagawa, Kazuyuki, Fujioka, Takafumi, Nagami, Kazuyoshi
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): TURNIPSEED, JAMES
• Application Number:
  US06/808,420
• Time in Patent Office: 956 Days
• Field of Search: 544/363, 514/253
• US Class Current: 514/253.07
• CPC Class Codes: C07D 215/38 Nitrogen atoms nitro radicals C07D215/18

Abstract

A carbostyril compound of the formula (I): ##STR1## wherein R¹ and R² are as defined or its pharmaceutically acceptable salt, composition containing the compound and processes for preparing the same are disclosed.

The compound is useful as a cardiotonic agent.

Claims

1. A carbostyril compound of the formula (I):

##STR56## wherein R¹ is a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyl-lower alkyl group, a phenyl-lower alkyl group which has, on the phenyl ring thereof, 1 to 3 substituents selected from among lower alkanoyloxy and hydroxy groups, a benzoyl group which may optionally be substituted, on the phenyl ring thereof, withn 1 to 3 substituents selected from the group consisting of nitro, unsubstituted or lower alkyl-substituted amino, phenyl-lower alkoxy, hydroxy, carboxy, phenyl-lower alkoxycarbonyl-lower alkoxy, lower alkanoyloxy, carboxy-lower alkoxy and lower alkyl-substituted amino-lower alkyl, or a naphthoyl group, R² is a benzoyl group which may optionally have, on the phenyl ring thereof, 1 or 2 lower alkoxy groups, and its pharmaceutically acceptable salt.

2. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 1, wherein R² is a benzoyl group which is substituted with 1 or 2 of a (C_1-6)alkoxy group.

3. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 2, wherein R¹ is a benzoyl group which may optionally be substituted, on the phenyl ring thereof, with 1 to 3 substituents selected from the group consisting of nitro, unsubstituted or (C_1-6)alkyl-substituted amino, phenyl-(C_1-6)alkoxy, hydroxy, carboxy, phenyl-(C_1-6)alkoxycarbonyl-(C_1-6)alkoxy, (C_1-6)alkanoyloxy, carboxy-(C_1-6)alkoxy, and (C_1-6)alkylsubstituted amino-(C_1-6)alkyl

4. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 2, wherein R¹ is a (C_1-6)alkanoyl group.

5. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 2, wherein R¹ is a (C_1-6)alkoxycarbonyl group, a (C_1-6)alkoxycarbonyl-(C_1-6)alkyl group, a phenyl-(C_1-6)alkyl group which has, on the phenyl ring thereof, 1 to 3 substitutent selected from among (C_1-6)alkanoyloxy and hydroxy groups, or a naphthoyl group.

6. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 3, wherein R¹ is a benzoyl group which is substituted, on the phenyl ring thereof, with 1 to 3 substituents selected from the group consisting of hydroxy, carboxy, unsubstituted or (C_1-6)alkyl-substituted amino, carboxy-(C_1-6)alkoxy, and (C_1-6)alkyl-substituted amino-(C_1-6)alkyl.

7. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 3, wherein R¹ is an unsubstituted benzoyl group.

8. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 6, wherein R¹ is a benzoyl group which is substituted, on the phenyl ring thereof, 1 to 2 substituents selected form the group consisting of unsubstituted or (C_1-6)alkyl-substituted amino, hydroxy, and carboxy-(C_1-6)alkoxy.

9. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 8, wherein R² is a 3,4-di(C_1-6)alkoxybenzoyl group.

10. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 9, wherein R¹ is a benzoyl group which is substituted, on the phenyl ring thereof, with one substituent selected form the group consisting of unsubstituted or (C_1-6)alkyl-substituted amino, and hydroxy.

11. 1-(4-Aminobenzoyl)-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril according to claim 10.

12. 1-(4-Hydroxybenzoyl)-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril according to claim 10.

13. 1-Benzxoyl-6-[4-(3,4-dimethoxybenzxoyl)-1-piperazinyl]-3,4-dihydrocarbostyril according to claim 7.

14. 1-(4-Hydroxy-3-dimethylaminomethylbenzxoyl)-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril according to claim 9.

15. 1-(3-Hydroxy-5-carboxymethoxybenzoyl)-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril according to claim 9.

16. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 5, wherein R¹ is a (C₁ -C₆) alkoxycarbonyl group.

17. A carbostyril compound of the formula (I):

##STR57## wherein R¹ is a lower alkanoyl group, a lower alkoxycarbonyl group, a benzoyl group which may optionally be substituted, on the phenyl ring thereof, with 1 to 2 substituents selected from the group consisting of unsubstituted amino, hydroxy, and carboxy, R² is a benzoyl group which may optionally have, on the phenyl ring thereof, 1 or 2 of a lower alkoxy group, and its pharmaceutically acceptable salt.

18. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 17, wherein R¹ is a benzoyl group which is substituted, on the phenyl ring thereof, 1 to 2 substituents selected from the group consisting of unsubstituted amino, hydroxy, and carboxy.

19. A carbostyril compound or its pharmaceutically acceptable salt as claimed in claim 18, wherein R¹ is a benzoyl group which is substituted, on the phenyl ring thereof, with one substituent selected from the group consisting of unsubstituted amino and hydroxy.

20. A cardiotonic composition comprising a cardiotonically effective amount of a compound of the formula (I):

##STR58## wherein R¹ is a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyl-lower alkyl group, a phenyl-lower alkyl group which has, on the phenyl ring thereof, 1 to 3 substituents selected from among lower alkanoyloxy and hydroxy groups, a benzoyl group which may optionally be substituted, on the phenyl ring thereof, with 1 to 3 substituents selected from the group consisting of nitro, unsubstituted or lower alkyl-substituted amino, phenyl-lower alkoxy, hydroxy, carboxy, phenyl-lower alkoxycarbonyl-lower alkoxy, lower alkanoyloxy, carboxyl-lower alkoxy, and lower alkyl-substituted amino-lower alkyl, or a naphthoyl group, R² is a benzoyl group which may optionally have, on the phenyl ring thereof, 1 or 2 lower alkoxy groups, and its pharmaceutically acceptable salt.