Carbostyril derivatives and pharmaceutical composition containing the same

• US 4,455,422 A
• Filed: 04/07/1982
• Issued: 06/19/1984
• Est. Priority Date: 03/06/1980
• 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: Nakagawa, Kazuyuki, Fujioka, Takafumi, Osaki, Masaaki, Banno, Kazuo
• Primary Examiner(s): Lee, Mary C.
• Assistant Examiner(s): Gibson, S. A.
• Application Number:
  US06/366,335
• Time in Patent Office: 804 Days
• Field of Search: 544/363, 542/444, 542/436, 542/439
• US Class Current: 544/363
• CPC Class Codes: C07D 215/227 only one oxygen atom which is attached in position 2

Abstract

Novel carbostyril derivatives and their salts, having antihistaminic effect and central nervous system controlling effect, are represented by the general formula (1), ##STR1## wherein R¹ is a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group, a lower alkenyl group, a lower alkynyl group; A is a group of the formula ##STR2## (wherein R² is a hydrogen atom or a lower alkyl group); B is a lower alkylene group; l is 1 when A is a group of the formula ##STR3## or l is 0 or 1 when A is a group of the formula ##STR4## Z is a group of the formula >N--R³ or ##STR5## (wherein R³, R⁴ and R⁵ are as defined herein).

Claims

1. A carbostyril derivative or salt thereof represented by the general formula (1), ##STR54## wherein R¹ is a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group, a lower alkenyl group or a lower alkynyl group;

R² is a hydrogen atom or a lower alkyl group;

B is a lower alkylene group;

l is 0 or 1;

R³ is an unsubstituted or a substituted-phenyl group having 1 to 3 substituents, on the phenyl ring, selected from the group consisting of a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkoxy-carbonyl group, a carboxy group, a lower alkylthio group, a lower alkanoyl group, a hydroxy group, a nitro group, an amino group and a cyano group;

or R³ is a substituted-phenyl group having a lower alkylenedioxy group as the substituent on the phenyl ring, a phenyl-lower alkyl group or 1,2,3,4-tetrahydronaphthyl group;

the carbon-carbon bond between 3- and 4-positions in the carbostyril skeleton is a single or double bond.

2. The carbostyril derivative or salt thereof according to claim 1, wherein R¹ is a hydrogen atom.

3. The carbostyril derivative or salt thereof according to claim 2, wherein the substituted position of a group of the formula, ##STR55## is at the 6-position in the carbostyril skeleton.

4. The carbostyril derivative or salt thereof according to claim 2, wherein the substituted position of a group of the formula, ##STR56## is at the 5-, 7- or 8-position in the carbostyril skeleton.

5. The carbostyril derivative or salt thereof according to claim 2, wherein R³ is an unsubstituted- or substituted phenyl group having 1 to 3 substituents, on the phenyl ring, selected from the group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group.

6. The carbostyril derivative or salt thereof according to claim 2, wherein R³ is a substituted-phenyl group having 1 to 3 substituents, on the phenyl ring, selected from the group consisting of a lower alkoxy-carbonyl group, a carboxy group, a lower alkylthio group, a lower alkanoyl group, a hydroxy group, a nitro group, an amino group and a cyano group.

7. The carbostyril derivative or salt thereof according to claim 2, wherein R³ is a substituted-phenyl group having a lower alkylenedioxy group as the substituent on the phenyl ring or a 1,2,3,4-tetrahydronaphthyl group.

8. The carbostyril derivative or salt thereof according to claim 2, wherein R³ is a phenyl-lower alkyl group.

9. The carbostyril derivative or salt thereof according to claim 5, wherein the substituted position of the group of the formula, ##STR57## is at the 6-position in the carbostyril skeleton.

10. The carbostyril derivative or salt thereof according to claim 5, wherein the substituted position of the group of the formula, ##STR58## is at the 5-, 7- or 8-position in the carbostyril skeleton.

11. The carbostyril derivative or salt thereof according to claim 6, wherein the substituted position of the group of the formula, ##STR59## is at the 6-position in the carbostyril skeleton.

12. The carbostyril derivative or salt thereof according to claim 7, wherein the substituted position of the group of the formula, ##STR60## is at the 6-position in the carbostyril skeleton.

13. The carbostyril derivative or salt thereof according to claim 8, wherein the substituted position of the group of the formula, ##STR61## is at the 6-position in the carbostyril skeleton.

14. The carbostyril derivative or salt thereof according to claim 1, wherein R¹ is a lower alkyl group, a phenyl-lower alkyl group, a lower alkenyl group, or a lower alkynyl group.

22. A central nervous system controlling agent containing at least one carbostyril derivative represented by the general formula (1) as claimed in claim 1 as the active ingredient.

15. 6-{4-[4-(3-Chlorophenyl)-1-piperazinyl]-1-butenyl}-3,4-dihydrocarbostyril.

16. 6-{3-[4-(2-Methoxyphenyl)-1-piperazinyl]-1-propenyl}-3,4-dihydrocarbostyril.

17. 6-[4-(4-Phenyl-1-piperazinyl)-1-butenyl]-3,4-dihydrocarbostyril.

18. 6- 3-[4-(3-Chlorophenyl)-1-piperazinyl]-1-propenyl-3,4-dihydrocarbostyril.

19. 6- 3-[4-(3-Methylphenyl)-1-piperazinyl]-1-propenyl-3,4-dihydrocarbostyril.

20. 6- 4-[4-(2,3-Dimethylphenyl)-1-piperazinyl]-1-butenyl-3,4-dihydrocarbostyril.

21. 6-[3-(4-Phenyl-1-piperazinyl)-1-propenyl]-3,4-dihydrocarbostyril.