Patent EP0396124A2 successfully refreshed from Google Patents.
EP0396124A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Compositions containing indole-2-carboxylate compounds for treatment of CNS disorders
Assignee: GD Searle LLC
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Filing: 1990-05-03
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Granted: —
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Expires: 2010-05-03
Abstract
Abstract Compositions containing certain indole-2-carboxylate compounds and derivatives are described as being therapeutically effective in treatment of CNS disorders resulting from neurotoxic damage or neurodegenerative diseases, particularly those CNS disorders resulting from ischemic events. Preferred compounds are of the formula wherein each of R 5 and R 6 is independently selected from hydrido, bromo, chloro and fluoro, and wherein each of R 10 and R 12 is independently selected from hydride and lower alkyl, and pharmaceutically-acceptable salts thereof.
Inventors
- 👤 Nancy M. Gray
- 👤 Brian K. Cheng
- 👤 William F. Hood
- 👤 Michael S. Dappen
- 👤 Alex A. Cordi
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 13:51
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/40; A61K31/403; A61K31/404; A61K31/405; A61P; A61P25/00; A61P25/08; A61P25/28; A61P9/00; A61P9/10
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
225 words
A pharmaceutical composition comprising a therapeutically-effective amount of an antineurotoxic compound and a pharmaceutically acceptable carrier or diluent, said antineurotoxic compound selected from a family of compounds of the formula wherein R' is selected from hydrido, alkyl and aralkyl; wherein each of R 2 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, cyano, alkylthio, sulfinyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, amino, monoalkylamino, dialkylamino, acyl, acyloxy, amido, aryloxy, aralkoxy, aralkoxyalkyl, aryl and , wherein R 9 is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through six; wherein X is selected from hydrido, halo, amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl; wherein Y is selected from hydrido, alkyl, hydroxy, halo, cycloalkyl, alkoxy, aryl and wherein R" is selected from hydrido, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through six; and wherein any of the foregoing X, Y and R' through R" substituents having a substitutable position is substituted with a radical selected from alkyl, halo, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monoaralkylamino, diaralkylamino, haloalkyl, aralkyl and aryl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 2
Dependent Claim
225 words
A pharmaceutical composition comprising a therapeutically-effective amount of an antineurotoxic compound and a pharmaceutically acceptable carrier or diluent, said antineurotoxic compound selected from a family of compounds of the formula wherein R' is selected from hydrido, alkyl and aralkyl; wherein each of R 2 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, cyano, alkylthio, sulfinyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, amino, monoalkylamino, dialkylamino, acyl, acyloxy, amido, aryloxy, aralkoxy, aralkoxyalkyl, aryl and , wherein R 9 is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through six; wherein X is selected from hydrido, halo, amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl; wherein Y is selected from hydrido, alkyl, hydroxy, halo, cycloalkyl, alkoxy, aryl and wherein R" is selected from hydrido, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through six; and wherein any of the foregoing X, Y and R' through R" substituents having a substitutable position is substituted with a radical selected from alkyl, halo, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monoaralkylamino, diaralkylamino, haloalkyl, aralkyl and aryl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 3
Dependent Claim
190 words
The composition of Claim 1 wherein R 1 is selected from hydrido, alkyl and aralkyl; wherein each of R 2 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, cyano, alkylthio, amino, monoalkylamino, dialkylamino, acyl, acyloxy, amido, aryloxy, aralkoxy, aralkoxyalkyl, aryl and wherein R 9 is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino; wherein n is a number selected from zero through four; wherein X is selected from halo, amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl; wherein Y is selected from hydroxy, halo, alkoxy and wherein R" is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through four; and wherein any of the foregoing X, Y and R 1 through R11 substituents having a substitutable position is substituted with a radical selected from alkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monophenylalkylamino, aralkyl and aryl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 4
Dependent Claim
199 words
The composition of Claim 2 wherein R 1 is selected from hydrido, alkyl and phenalkyl; wherein each of R 2 and R 3 ' is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, phenylalkyl, amino, monoalkylamino, dialkylamino, and phenyl; wherein each of R 4 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, phenalkyl, phenoxy, benzyloxy, phenethyloxy, amino, monoalkylamino, dialkylamino, acyloxy, phenyl and wherein R 9 is selected from hydrido, hydroxy, alkyl, alkoxy, phenyl, phenoxy, phenalkyl, phenalkyloxy, amino. monoalkylamino, and dialkylamino wherein n is a number selected from zero through four; wherein X is selected from amino, monoalkylamino, dialkylamino and OR 10 wherein R' o is selected from hydrido, halo, alkyl, phenalkyl and phenyl; wherein Y is selected from hydroxy, halo, alkoxy and wherein R 11 is selected from hydrido, hydroxy, alkyl, alkoxy, phenyl, phenoxy, phenalkyl, phenalkyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through six; and wherein any of the foregoing X, Y and R' through R" substituents having a substitutable position is substituted with a radical selected from alkyl, hydroxy, alkoxy, amino, monoalkylamino. dialkylamino, monophenalkylamino, phenalkyl and phenyl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 5
Dependent Claim
196 words
The composition of Claim 3 wherein R 1 is selected from hydrido and lower alkyl; and wherein each of R 2 and R 3 is independently selected from hydrido, halo, lower alkyl, benzyl and phenyl; wherein each of R 4 through R 7 is independently selected from hydrido, halo, hydroxy, lower alkyl, haloalkyl, lower alkoxy, phenoxy, benzyloxy, benzyl, phenyl, and wherein R 9 is selected from hydrido, hydroxy, lower alkyl, lower alkoxy, phenyl, phenoxy, benzyl, benzyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through two; wherein X is selected from amino, monoalkylamino, dialkylamino and OR'° wherein R 10 is selected from hydrido, lower alkyl, benzyl and phenyl; wherein Y is selected from hydroxy, halo, lower alkoxy, benzyloxy and wherein R 11 is selected from hydrido, hydroxy, lower alkyl, lower alkoxy, phenyl, phenoxy, benzyl, benzyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through four; and wherein any of the foregoing X, Y and R' through R" substituents having a substitutable position is substituted with a radical selected from lower alkyl, hydroxy, lower alkoxy, benzyl, amino, monoalkylamino, dialkylamino, monophenalkylamino and phenyl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 6
Dependent Claim
84 words
The composition of Claim 4 wherein said antineurotoxic compound is of the formula wherein each of R 5 and R 6 is independently selected from hydrido, halo, lower alkyl, haloloweralkyl and lower alkoxy; and wherein R 10 is selected from hydrido, lower alkyl, benzyl and phenyl: wherein Y is selected from hydroxy, lower alkoxy, benzyloxy and wherein R" is selected from hydrido, hydroxy, lower alkyl, lower alkoxy, amino, monoalkylamino, dialkylamino, monophenalkylamino and phenyl; wherein m is one or two; or a pharmaceutically-acceptable salt thereof.
Claim 7
Dependent Claim
55 words
The composition of Claim 5 wherein said antineurotoxic compound is of the formula wherein each of R 5 and R 6 is independently selected from hydrido, fluoro, chloro and bromo; wherein R 10 is selected from hydrido and lower alkyl; wherein R 12 is selected from hydrido and lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 8
Dependent Claim
33 words
The composition of Claim 5 wherein said antineurotoxic compound is selected from 2-carboxy-3-indoleacetic acid; 2-carboxy-1-methyl-3-indoleacetic acid; 2-carboxy-5-chloro-3-indoleacetic acid; 5-bromo-2-carboxy-3-indoleacetic acid; 2-carboxy-5-fluoro-3-indoleacetic acid; ethyl 2-carboxy-6-chloro-3-indoleacetate; 2-carboxy-6-chloro-3-indoleacetamide; 2-carboxy-6-chloro-3-indoleacetic acid 3-ethylamide; ethyl 6-chloro-3-(2-chloroethyl)-2-indolecarboxylate; and 2-carboxy-6-chloro-3-indoleacetic acid.
Claim 9
Dependent Claim
12 words
The composition of Claim 7 wherein said antineurotoxic compound is 2-carboxy-6-chloro-3-indoleacetic acid.
Claim 10
Dependent Claim
221 words
Use of a therapeutically-effective amount of a compound of a formula wherein R' is selected from hydrido, alkyl and aralkyl; wherein each of R 2 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, cyano, alkylthio, sulfinyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, amino, monoalkylamino, dialkylamino, acyl, acyloxy, amido, aryloxy, aralkoxy, aralkoxyalkyl, aryl and , wherein R 9 is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through six; wherein X is selected from hydrido, halo, amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl; wherein Y is selected from hydrido, alkyl, hydroxy, halo, cycloalkyl, alkoxy, aryl and wherein R" is selected from hydrido, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino: wherein m is a number selected from zero through six; and wherein any of the foregoing X, Y and R 1 through R" substituents having a substitutable position is substituted with a radical selected from alkyl, halo, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monoaralkylamino, diaralkylamino, haloalkyl, aralkyl and aryl; or a pharmaceutically-acceptable salt or ester thereof for preparing a medicament for treating a neurodegenerative disease or neurotoxic jury in mammal.
Claim 11
Dependent Claim
221 words
Use of a therapeutically-effective amount of a compound of a formula wherein R' is selected from hydrido, alkyl and aralkyl; wherein each of R 2 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, cyano, alkylthio, sulfinyl, sulfonyl, sulfinylalkyl, sulfonylalkyl, amino, monoalkylamino, dialkylamino, acyl, acyloxy, amido, aryloxy, aralkoxy, aralkoxyalkyl, aryl and , wherein R 9 is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through six; wherein X is selected from hydrido, halo, amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl; wherein Y is selected from hydrido, alkyl, hydroxy, halo, cycloalkyl, alkoxy, aryl and wherein R" is selected from hydrido, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino: wherein m is a number selected from zero through six; and wherein any of the foregoing X, Y and R 1 through R" substituents having a substitutable position is substituted with a radical selected from alkyl, halo, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monoaralkylamino, diaralkylamino, haloalkyl, aralkyl and aryl; or a pharmaceutically-acceptable salt or ester thereof for preparing a medicament for treating a neurodegenerative disease or neurotoxic jury in mammal.
Claim 12
Dependent Claim
190 words
Use according to Claim 9 wherein R 1 is selected from hydrido, alkyl and aralkyl; wherein each of R 2 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aralkyl, alkoxyalkyl, cyano, alkylthio, amino, monoalkylamino, dialkylamino, acyl, acyloxy, amido, aryloxy, aralkoxy, aralkoxyalkyl, aryl and wherein R 9 is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through four; wherein X is selected from halo, amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl and aryl; wherein Y is selected from hydroxy, halo, alkoxy and wherein R" is selected from hydrido, halo, hydroxy, alkyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, aryl, aryloxy, aralkyl, aralkyloxy, amino, monoalkylamino and dialkylamino: wherein m is a number selected from zero through four; and wherein any of the foregoing X, Y and R' through R 11 substituents having a substitutable position is substituted with a radical selected from alkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monophenylalkylamino, aralkyl and aryl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 13
Dependent Claim
196 words
Use according to Claim 10 wherein R' is selected from hydrido, alkyl and phenalkyl; wherein each of R 2 and R 3 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, phenalkyl, amino, monoalkylamino, dialkylamino, and phenyl; wherein each of R4 through R 7 is independently selected from hydrido, halo, hydroxy, alkyl, haloalkyl, alkoxy, hydroxyalkyl, phenalkyl, phenoxy, benzyloxy, phenethyloxy, amino, monoalkylamino, dialkylamino, acyloxy, phenyl and wherein R 9 is selected from hydrido, hydroxy, alkyl, alkoxy, phenyl, phenoxy, phenalkyl, phenalkyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through four; wherein X is selected from amino, monoalkylamino, dialkylamino and OR 10 wherein R 10 is selected from hvdrido, halo, alkyl, phenalkyl and phenyl; wherein Y is selected from hydroxy, halo, alkoxy and wherein R" is selected from hydrido, hydroxy, alkyl, alkoxy, phenyl, phenoxy, phenalkyl, phenalkyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through six; and wherein any of the foregoing X, Y and R 1 through R" substituents having a substitutable position is substituted with a radical selected from alkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, monophenalkylamino, phenalkyl and phenyl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 14
Dependent Claim
196 words
Use according to Claim 11 wherein R' is selected from hydrido and lower alkyl; and wherein each of R 2 and R 3 is independently selected from hydrido, halo, lower alkyl, benzyl and phenyl; wherein each of R 4 through R 7 is independently selected from hydrido, halo, hydroxy, lower alkyl, haloalkyl, lower alkoxy, phenoxy, benzyloxy, benzyl, phenyl, and wherein R 9 is selected from hydrido, hydroxy, lower alkyl, lower alkoxy, phenyl, phenoxy, benzyl, benzyloxy, amino, monoalkylamino and dialkylamino, wherein n is a number selected from zero through two; wherein X is selected from amino, monoalkylamino, dialkylamino and OR'° wherein R 10 is selected from hydrido, lower alkyl, benzyl and phenyl; wherein Y is selected from hydroxy, halo, lower alkoxy, benzyloxy and wherein R 11 is selected from hydrido, hydroxy, lower alkyl, lower alkoxy, phenyl, phenoxy, benzyl, benzyloxy, amino, monoalkylamino and dialkylamino; wherein m is a number selected from zero through four; and wherein any of the foregoing X, Y and R 1 through R" substituents having a substitutable position is substituted with a radical selected from lower alkyl, hydroxy, lower alkoxy, benzyl, amino, monoalkylamino, dialkylamino, monophenalkylamino and phenyl; or a pharmaceutically-acceptable salt or ester thereof.
Claim 15
Dependent Claim
83 words
Use according to Claim 12 wherein said compound is of the formula wherein each of R 5 and R 6 is independently selected from hydrido, halo, lower alkyl, haloloweralkyl and lower alkoxy; and wherein R 10 is selected from hydrido, lower alkyl, benzyl and phenyl; wherein Y is selected from hydroxy, lower alkoxy, benzyloxy and wherein R" is selected from hydrido, hydroxy, lower alkyl, lower alkoxy, amino, monoalkylamino, dilkylamino, monophenalkylamino and phenyl; wherein m is one or two; or a pharmaceutically-acceptable salt thereof.
Claim 16
Dependent Claim
54 words
Use according to Claim 13 wherein said compound is of the formula wherein each of R 5 and R 6 is independently selected from hydrido, fluoro, chloro and bromo; wherein R' o is selected from hydrido and lower alkyl; wherein R 12 is selected from hydrido and lower alkyl; or a pharmaceutically-acceptable salt thereof.
Claim 17
Dependent Claim
32 words
Use according to Claim 13 wherein said compound is selected from 2-carboxy-3-indoleacetic acid; 2-carboxy-1-methyl-3-indoleacetic acid; 2-carboxy-5-chloro-3-indoleacetic acid; 5-bromo-2-carboxy-3-indoleacetic acid; 2-carboxy-5-fluoro-3-indoleacetic acid; ethyl 2-carboxy-6-chloro-3-indoleacetate; 2-carboxy-6-chloro-3-indoleacetamide; 2-carboxy-6-chloro-3-indoleacetic acid 3-ethylamide; ethyl 6-chloro-3-(2-chloroethyl)-2-indolecarboxylate; and 2-carboxy-6-chloro-3-indoleacetic acid.
Claim 18
Dependent Claim
11 words
Use according to Claim 15 wherein said compound is 2-carboxy-6-chloro-3-indoleacetic acid.
References Cited (Backward Citations)
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