EP0037231A2
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EP
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Substituted acyl derivatives of octahydro-1H-indole-2-carboxylic acids
Assignee: Warner Lambert Co LLC
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Filing: 1981-03-24
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Granted: —
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Expires: 2001-03-24
Abstract
Abstract Octahydro-1-(w-mercaptoalkanoyl)-1H-indole-2-carboxylic acid compounds having the formula wherein R is hydrogen or lower alkyl; R 1 is hydrogen, lower 0 alkyl, or benzyl; R 2 is hydrogen or R 3- C- where R 3 is lower alkyl, heteroaryl containing 4 to 9 carbon atoms and one or two nitrogen, oxygen or sulfur atoms; phenyl, substituted phenyl having 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, lower alkyl or alkoxy; and n is 0 or 1; wherein lower alkyl and lower alkoxy include straight or branched groups containing 1 to 4 carbon atoms, and pharmaceutically acceptable salts of the compounds when R is hydrogen and when R 3 is heteroaryl containing 1 or 2 nitrogen atoms, are disclosed. Also disclosed are substituted acyl compounds of octahydro-lH-indole-2-carboxylic acid having the formula wherein R 4 is hydrogen or lower alkyl; R 5 is hydrogen, lower alkyl or benzyl; R 6 is hydrogen or lower alkyl; Ar is phenyl or phenyl substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, lower alkyl, lower alkoxy, hydroxy or amino; and m is 0 to 3; wherein lower alkyl and lower alkoxy contain 1 to 4 straight or branched carbon atoms; and the pharmaceutically acceptable salts thereof. The compounds and the salts are useful for treating hypertension.
Inventors
- 👤 Milton Louis Hoefle
- 👤 George Bobowski
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-30 00:08
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/30; C07D209/42; A; A61; A61P; A61P9/00; A61P9/12; C07K; C07K5/00; C07K5/02; C07K5/022; C07K5/0222; C07K5/04; C07K5/06; C07K5/06008; C07K5/06017; C07K5/06026; C07K5/06034; C07K5/06078; A61K; A61K38/00
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
113 words
An octahydro-1-(ω-mercaptoalkanoyl)-1H-indole-2-carboxylic acid compound having the formula wherein R is hydrogen or lower alkyl; R 1 is hydrogen, lower alkyl or benzyl; R 2 is hydrogen or (wherein R 3 is lower alkyl, heteroaryl containing 4 to 9 carbon atoms and one or two nitrogen, oxygen or sulphur atoms, phenyl, substituted phenyl having one or two substituents selected from fluorine, chlorine, bromine, lower alkyl and alkoxy); and n is 0 or 1; wherein lower alkyl and lower alkoxy include straight or branched groups containing 1 to 4 carbon atoms; or a pharmaceutically acceptable salt of the compound when R is hydrogen and when R 3 is heteroaryl containing 1 or 2 nitrogen atoms.
Claim 2
Dependent Claim
113 words
An octahydro-1-(ω-mercaptoalkanoyl)-1H-indole-2-carboxylic acid compound having the formula wherein R is hydrogen or lower alkyl; R 1 is hydrogen, lower alkyl or benzyl; R 2 is hydrogen or (wherein R 3 is lower alkyl, heteroaryl containing 4 to 9 carbon atoms and one or two nitrogen, oxygen or sulphur atoms, phenyl, substituted phenyl having one or two substituents selected from fluorine, chlorine, bromine, lower alkyl and alkoxy); and n is 0 or 1; wherein lower alkyl and lower alkoxy include straight or branched groups containing 1 to 4 carbon atoms; or a pharmaceutically acceptable salt of the compound when R is hydrogen and when R 3 is heteroaryl containing 1 or 2 nitrogen atoms.
Claim 3
Dependent Claim
62 words
A compound according to claim 1 having the formula wherein R 1 is hydrogen or lower alkyl containing 1 to 3 carbon atoms; R 2 is hydrogen or (wherein R 3 is lower alkyl containing 1 to 3 carbon atoms, phenyl, furyl, benzo(b)furyl, thienyl, benzo(b) thienyl, pyridyl, quinolyl or isoquinolyl); and n is 0 or 1; or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
34 words
A compound according to claim 2, wherein R 1 is hydrogen or methyl; and wherein R 2 is hydrogen or (wherein R 3 is methyl or phenyl); or a pharmaceutially acceptable basic salt thereof.
Claim 5
Dependent Claim
101 words
A compound according to claim 3, being the compound octahydro-1-(3-(acetylthio)-2-methylpropanoyl]-1H-indole-2-carboxylic acid or a pharmaceutically acceptable basic salt thereof; or the compound octahydro-1-(3-mercapto-2-methylpropanoyl)-lH-indole-2-carboxylic acid or a pharmaceutically acceptable basic salt thereof; or the compound (2a, 3aB, 7aβ)-octahydro-1-(3-mercapto-2-methyl-propanoyl)-lH-indole-2-carboxylic acid or a pharmaceutically acceptable basic salt thereof; or the compound (2a, 3aβ, 7aβ)-octahydro-1-(3-mercapto-2-methyl-propanoyl)-lH-indole-2-carboxylic acid, diastereomer A, or a pharmaceutically acceptable basic salt thereof; or the compound (1)-(2α, 3aB, 7aβ)-octahydro-1-(3-mercapto-2-methyl-propanoyl)-lH-indole-2-carboxylic acid, diastereomer A, or a pharmaceutically acceptable basic salt thereof; or the compound octahydro-1-(3-mercaptopropanoyl) -lH-indole-2-carboxylic acid or a pharmaceutically acceptable basic salt thereof; or the compound octahydro-1-[3-(acetylthio)propanoyl]-1H-indole-2-carboxylic acid or a pharmaceutically acceptable basic salt thereof.
Claim 6
Dependent Claim
82 words
A process for the production of a substituted octahydro-1-(ω-mercaptoalkanoyl)-1-indole-2-carboxylic acid compound according to claim 1, which comprises acylating an ethyl or trimethylsilyl ester or an acid salt of a tertiary amine or alkali metal of octahydro-1H-indole-2-carboxylic acid with an appropriate acid halide of the formula wherein R 1 , R 3 and n are as defined in claim 1 and X is halogen, and hydrolyzing with base to obtain a compound according to claim 1 wherein R and R 2 are hydrogen.
Claim 7
Dependent Claim
24 words
A pharmaceutical composition comprising a substituted octahydro-1-(3-mercaptoalkanoyl)-1-indole-2-carboxylic acid compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Claim 8
Dependent Claim
86 words
A substituted acyl derivative of octahydro-lH-indole-2-carboxylic acid having the formula wherein R 4 is hydrogen or lower alkyl, R 5 is hydrogen, lower alkyl or benzyl, R 6 is hydrogen or lower alkyl, Ar is phenyl or phenyl substituted with one or two substituents selected from fluorine, chlorine, bromine, lower alkyl, lower alkoxy, hydroxy and amino, and m is 0 to 3; and wherein lower alkyl and lower alkoxy include straight and branched groups containing 1 to 4 carbon atoms; or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
86 words
A substituted acyl derivative of octahydro-lH-indole-2-carboxylic acid having the formula wherein R 4 is hydrogen or lower alkyl, R 5 is hydrogen, lower alkyl or benzyl, R 6 is hydrogen or lower alkyl, Ar is phenyl or phenyl substituted with one or two substituents selected from fluorine, chlorine, bromine, lower alkyl, lower alkoxy, hydroxy and amino, and m is 0 to 3; and wherein lower alkyl and lower alkoxy include straight and branched groups containing 1 to 4 carbon atoms; or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
62 words
A derivative according to claim 7, having the formula wherein R 5 is hydrogen or lower alkyl containing 1 to 3 carbon atoms, R 6 is hydrogen or lower alkyl containing 1 to 3 carbon atoms, and Ar is phenyl or phenyl substituted in the para position by fluorine, chlorine, bromine, methyl, hydroxy, methoxy or amino; or a pharmaceutically acceptable salt thereof.
Claim 11
Dependent Claim
29 words
A derivative according to claim 8, having the formula wherein R 6 is hydrogen or lower alkyl containing 1 to 3 carbon atoms, or a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
40 words
A derivative according to claim 9, being the compound 1-(2-[(1-carboxy-3-phenylpropyl)amino)-1-oxopropyl]-octahydro-1H-indole-2-carboxylic acid or a pharmaceutically acceptable salt thereof; or the compound 1-[2-[(1-carbomethoxy-3-phenylpropyl)amino]-1-oxopropyl]octahydro- lH-indole-2-carboxylic acid or a pharmaceutically acceptable salt thereof; or the compound 1-[2-[(1-carboethoxy-3-phenylpropyl)amino]-1-oxopropyl)-octahydro-1H-indole-2-carboxylic acid or a pharmaceutically acceptable salt thereof.
Claim 13
Dependent Claim
66 words
A process for the production of a substituted acyl derivative of octahydro-1H-indole-2-carboxylic acid according to claim 7, which comprises peptide coupling of a protected octahydro-lH-indole-2-carboxylate of formula - wherein R 7 is a protected carboxylic acid group, with an N-substituted-amino acid of the formula where R5, Ar and m are as defined in claim 7 and R 6 is lower alkyl, and removing the protective group.
Claim 14
Dependent Claim
26 words
A pharmaceutical composition comprising a substituted acyl derivative of octahydro-1H-indole-2-carboxylic acid according to claim 7, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
References Cited (Backward Citations)
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