US5464833A
Expired / Lapsed
US
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Apoptosis regulating composition
Assignee: Otsuka Pharmaceutical Co Ltd
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Filing: 1993-08-12
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Granted: 1995-11-07
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Expires: 2013-08-12
Abstract
Abstract Apoptosis regulating compositions each comprising a member selected from a series of carbostyril derivatives and salts thereof, inclusive of carbostyril derivatives of general formula (1) ##STR1## and salts thereof, as an active ingredient are provided. The apoptosis regulating compositions of the invention are of use as anticancer agents, antiretrovirus agents, therapeutic agents for autoimmune diseases, therapeutic agents for thrombocytopenia, therapeutic agents for Alzheimer's disease, therapeutic agents for diseases of the liver, and cancer metastasis inhibitors, among others.
Inventors
- 👤 Satoru Nakai
- 👤 Koutoku Aihara
- 👤 Hideo Tanaka
- 👤 Hitomi Iba
- 👤 Kazuyoshi Kawai
- 👤 Hiroyuki Ichikawa
- 👤 Seiji Akamatsu
- 👤 Fumio Saito
- 👤 Michiaki Tominaga
- 👤 Masakazu Adachi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 03:20
CPC Classifications
C; C07; C07D; C07D215/00; C07D215/02; C07D215/16; C07D215/20; C07D215/22; C07D215/227; C07D215/38
Claims Analysis
Total Claims: 7
Claim 1
Independent Claim
599 words
A method for regulating apoptosis in a host in need of such regulation which comprises administering to said host an apoptosis regulating effective amount of at least one compound selected from the group consisting of the following carbostyril derivatives or salts thereof as an active ingredient together with a pathologically acceptable carrier: (1) Carbostyril derivatives of the following general formula ##STR9## wherein R is a benzoyl group which may optionally have, on the phenyl ring thereof, one to three substituents each selected from the group consisting of lower alkoxy groups, halogen atoms, lower alkyl groups, lower alkanoylamino group and lower alkylthio groups; a lower alkylenedioxybenzoyl group; a hydrogen atom; a pyridylcarbonyl group; a lower alkanesulfonyl group; a lower alkynyl group; or a phenyl-lower alkyl group which may optionally have, on the phenyl ring thereof, one to three substituents each selected from the group consisting of lower alkoxy groups, halogen atoms and lower alkyl groups; the carbon-carbon bond between the 3 and 4 positions of the carbostyril skeleton is a single bond or a double bond; R 20 is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or a phenyl-lower alkyl group; and R 21 is a hydrogen atom or a lower alkoxy group; provided that when both R 20 and R 21 are hydrogen atoms, R should not be a benzoyl group having a lower alkoxy group as a phenyl ring substituent; and salts thereof; (2) Carbostyril derivatives of the following general formula ##STR10## wherein R 1 is a group of the formula ##STR11## R 3 is a hydrogen atom or a benzoyl group; R 4 is an oxo group; and the carbon-carbon bond between the 3 and 4 positions of the carbostyril skeleton is a single bond or a double bond; and salts thereof; (3) Carbostyril derivatives of the following general formula ##STR12## wherein R 5 is a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyl-lower alkyl group, a phenyl-lower alkyl group having a lower alkanoyloxy group or a hydroxyl group on the phenyl ring thereof, or a benzoyl group which may optionally have, on the phenyl ring thereof, at least one substituent selected from the group consisting of a hydroxyl group and amino groups optionally having a lower alkyl group, or a naphthoyl group; and R 6 is a benzoyl group which may optionally have at least one lower alkoxy group on the phenyl ring thereof; and salts thereof; (4) Carbostyril derivatives of the following general formula ##STR13## wherein R 7 is a piperazinyl group, R 8 is a hydrogen atom or a lower alkyl group; R 9 is a hydrogen atom or a phenyl-lower alkyl group; and the carbon-carbon bond between the 3 and 4 positions of the carbostyril skeleton is a single bond or a double bond; and salts thereof; (5) Carbostyril derivatives of the following general formula ##STR14## wherein R 22 is a C 1 -C 16 alkyl group, a phenyl-lower alkoxycarbonyl-lower alkyl group, an amido-lower alkyl group which may optionally have at least one lower alkyl group, or a phenyl-lower alkyl group; and R 23 is a piperazinyl group which may optionally have a lower alkyl group in the 4 position of the piperazine ring; and salts thereof; (6) Carbostyril derivatives of the following general formula ##STR15## wherein R 24 is a hydrogen atom, a phenyl-lower alkyl group, a benzoyl-lower alkyl group, or a benzoyl group which may optionally have one to three lower alkoxy groups or lower alkylenedioxy groups on the phenyl ring thereof; and salts thereof; and (7) 6-[4-(3,4-Dimethoxybenzoyl)-1-1,2,3,4-tetrahydropirazyl]-3,4-dihydrocarbostyril and salts thereof.
Claim 2
Independent Claim
599 words
A method for regulating apoptosis in a host in need of such regulation which comprises administering to said host an apoptosis regulating effective amount of at least one compound selected from the group consisting of the following carbostyril derivatives or salts thereof as an active ingredient together with a pathologically acceptable carrier: (1) Carbostyril derivatives of the following general formula ##STR9## wherein R is a benzoyl group which may optionally have, on the phenyl ring thereof, one to three substituents each selected from the group consisting of lower alkoxy groups, halogen atoms, lower alkyl groups, lower alkanoylamino group and lower alkylthio groups; a lower alkylenedioxybenzoyl group; a hydrogen atom; a pyridylcarbonyl group; a lower alkanesulfonyl group; a lower alkynyl group; or a phenyl-lower alkyl group which may optionally have, on the phenyl ring thereof, one to three substituents each selected from the group consisting of lower alkoxy groups, halogen atoms and lower alkyl groups; the carbon-carbon bond between the 3 and 4 positions of the carbostyril skeleton is a single bond or a double bond; R 20 is a hydrogen atom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group or a phenyl-lower alkyl group; and R 21 is a hydrogen atom or a lower alkoxy group; provided that when both R 20 and R 21 are hydrogen atoms, R should not be a benzoyl group having a lower alkoxy group as a phenyl ring substituent; and salts thereof; (2) Carbostyril derivatives of the following general formula ##STR10## wherein R 1 is a group of the formula ##STR11## R 3 is a hydrogen atom or a benzoyl group; R 4 is an oxo group; and the carbon-carbon bond between the 3 and 4 positions of the carbostyril skeleton is a single bond or a double bond; and salts thereof; (3) Carbostyril derivatives of the following general formula ##STR12## wherein R 5 is a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxycarbonyl-lower alkyl group, a phenyl-lower alkyl group having a lower alkanoyloxy group or a hydroxyl group on the phenyl ring thereof, or a benzoyl group which may optionally have, on the phenyl ring thereof, at least one substituent selected from the group consisting of a hydroxyl group and amino groups optionally having a lower alkyl group, or a naphthoyl group; and R 6 is a benzoyl group which may optionally have at least one lower alkoxy group on the phenyl ring thereof; and salts thereof; (4) Carbostyril derivatives of the following general formula ##STR13## wherein R 7 is a piperazinyl group, R 8 is a hydrogen atom or a lower alkyl group; R 9 is a hydrogen atom or a phenyl-lower alkyl group; and the carbon-carbon bond between the 3 and 4 positions of the carbostyril skeleton is a single bond or a double bond; and salts thereof; (5) Carbostyril derivatives of the following general formula ##STR14## wherein R 22 is a C 1 -C 16 alkyl group, a phenyl-lower alkoxycarbonyl-lower alkyl group, an amido-lower alkyl group which may optionally have at least one lower alkyl group, or a phenyl-lower alkyl group; and R 23 is a piperazinyl group which may optionally have a lower alkyl group in the 4 position of the piperazine ring; and salts thereof; (6) Carbostyril derivatives of the following general formula ##STR15## wherein R 24 is a hydrogen atom, a phenyl-lower alkyl group, a benzoyl-lower alkyl group, or a benzoyl group which may optionally have one to three lower alkoxy groups or lower alkylenedioxy groups on the phenyl ring thereof; and salts thereof; and (7) 6-[4-(3,4-Dimethoxybenzoyl)-1-1,2,3,4-tetrahydropirazyl]-3,4-dihydrocarbostyril and salts thereof.
Claim 3
Dependent Claim
14 words
The method according claim 1, wherein said host is a human afflicted with cancer.
Claim 4
Dependent Claim
17 words
The method according to claim 1, wherein said host is a human afflicted with a retrovirus-related disease.
Claim 5
Dependent Claim
18 words
The method according to claim 1, wherein said host is a human in need of cytokine production inhibition.
Claim 6
Dependent Claim
19 words
The method according to claim 1, wherein said host is a human in need of peripheral lymphocyte activation inhibition.
Claim 7
Dependent Claim
17 words
The method according to claim 1, wherein said host is a human afflicted with an autoimmune disease.
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