Patent US5276482A successfully refreshed from Google Patents.
EP0021883A2
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EP
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N-acyl-amino acid derivatives and pharmaceutical compositions containing them, intermediates and starting compounds
Assignee: Merrell Toraude et Cie
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Filing: 1980-05-27
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Granted: —
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Expires: 2000-05-27
Abstract
Abstract ovel N-acyl amino acid derivatives are irreversible inhibitors of angiotensin-converting enzyme and have the following general Formula 1:- wherein:- Z represents an electron-withdrawing group, preferably cyano or a carbonyl-terminated functional group; X represents a group which, in combination with Z, can form a Michael acceptor after abstraction of the proton from the carbon atom adjacentto X, and preferably X is ethynyl or a fluoromethyl group; R, represents hydrogen, alkyl or phenylalkyl; and R 2 represents an aminocarboxylic acid residue obtained by removal of a hydrogen atom from the amino group thereof. Novel intermediates include compounds of the following general Formula 21:- wherein A represents tert-butyl, dibenzyl or trityl, and compounds of the following general Formula 36 (being the combination of Formulae 29 and 35 herein):- wherein X 1 represents ethynyl or mono-, di- or trifluoromethyl; R 1 is a defined above; R e represents hydroxy, alkoxy or amino; and R 10 represents hydrogen, alkyl, phenylalkyl, phenyl or p-methoxyphenyl.
Inventors
- 👤 Philippe Bey
- 👤 Brian Walter Metcalf
- 👤 Jeffrey Stewart Wiseman
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 15:24
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/44; C07D209/48; A; A61; A61P; A61P43/00; C07C; C07C321/00; C07C59/00; C07C59/40; C07C59/58; C07D207/00; C07D207/02; C07D207/04; C07D207/10; C07D207/16; C07D339/00; C07D339/08; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/0803; C07F7/081
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
66 words
A compound of the following general Formula 1:- wherein:- Z represents a cyano or a carbonyl-terminated electron-withdrawing group; X represents ethynyl, monofluoromethyl, difluoromethyl or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl, or phenyl-C 1 -C 7 alkyl; and R 2 represents an aminocarboxylic acid residue obtained by removal of a hydrogen atom from the amino group thereof, and salts, amides and esters thereof.
Claim 2
Dependent Claim
66 words
A compound of the following general Formula 1:- wherein:- Z represents a cyano or a carbonyl-terminated electron-withdrawing group; X represents ethynyl, monofluoromethyl, difluoromethyl or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl, or phenyl-C 1 -C 7 alkyl; and R 2 represents an aminocarboxylic acid residue obtained by removal of a hydrogen atom from the amino group thereof, and salts, amides and esters thereof.
Claim 3
Dependent Claim
11 words
A compound as claimed in Claim 1 wherein X represents ethynyl.
Claim 4
Dependent Claim
14 words
A compound as claimed in Claim 1 wherein X represents monofluoromethyl, difluoromethyl or trifluoromethyl.
Claim 5
Dependent Claim
15 words
A compound as claimed in any one of the preceding Claims wherein Z represents cyano.
Claim 6
Dependent Claim
89 words
A compound as claimed in any one of Claims 1 to 4 wherein Z represents cyano or a carbonyl-terminated group of the formula -COR wherein:- R represents R 2 is as defined in Claim 1; R 10 represents hydrogen, C 1 -C 7 alkyl, phenyl-C 1 -C 7 alkyl, phenyl or p-methoxyphenyl; R 11 represents halogen, . -SR 10 , tos y lox y , or -NH.CO.R 12 ; R 12 represents C 1 -C 7 alkyl, phenyl-C 1 -C 7 alkyl, phenyl, and n represents 3 or 4.
Claim 7
Dependent Claim
104 words
A compound as claimed in any one of the preceding Claims having the following general Formula 2:- wherein:- Z 1 represents cyano or a carbonyl-terminated electron-withdrawing group; X 1 represents ethynyl or mono-, di- or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl or phenyl-C l -C 7 alkyl; R 3 and R 4 represent hydrogen or the side chain of a naturally occurring mammalian amino acid of the formula and R 5 represents hydroxy, C 1 -C 7 alkoxy, primary amino or in which R 32 R 4 and R 5 are as defined above, and pharmaceutically acceptable salts thereof. -
Claim 8
Dependent Claim
158 words
A compound as claimed in any one of Claims 1 to 5 having the following general Formula 5:- wherein:- Z 1 represents cyano or an electron-withdrawing carbonyl-terminated functional group; X 1 represents ethynyl or mono-, di- or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl or phenyl-C 1 -C 7 alkyl; R 3 ' represents hydrogen and R 4 ' represents hydrogen or C 1 -C 4 alkyl and optionally substituted by indole, by imidazole or by phenyl, or R 3 ' and R 4 ' together represent alkylene or alkenylene, said alkylene and alkenylene having 2, 3 or 4 chain carbon atoms and being optionally substituted by hydroxy, by C 1 -C 7 alkyl or, in the hydrocarbon chain, by a sulfur atom; and R 5 ' represents hydroxy, C 1 -C 7 alkoxy, primary amino, or in which R 3' , R4' and R 5' are as defined above, and pharmaceutically acceptable salts thereof.
Claim 9
Dependent Claim
54 words
A compound as claimed in any one of the preceding Claims wherein RCO- represents -COR 10' , -CONHOH or -COCH(R 10 ")NHCOR 10 ' wherein R 10' represents C 1 -C 7 alkyl, phenyl or phenyl-C 1 -C 7 alkyl and Rio" represents C 1 -C 7 alkyl or phenyl-C 1 -C 7 alkyl.
Claim 10
Dependent Claim
31 words
A compound as claimed in Claim 8 wherein R 10' represents C 1 -C 4 alkyl, phenyl or benzyl and R 10 " represents C 1 -C 4 alkyl or benzyl.
Claim 11
Dependent Claim
144 words
A compound as claimed in any one of the preceding Claims having the following general Formula wherein:- Z 2 represents cyano, -COR 10' , -CO.NH.OH or X 1 represents ethynyl or mono-, di- or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl or phenyl-C 1 -C 7 alkyl; R 5 " represents hydroxy, C 1 -C 7 alkoxy or primary amino; m. represents 1, 2 or 3; each R 6 independently represents hydrogen, hydroxy or C 1 -C 7 alkyl or, when m represents 2 or 3, R 6 in each of two adjacent carbon atoms together represent a second valency bond between those carbon atoms; R 10' represents C 1 -C 7 alkyl, phenyl-C 1 -C 7 alkyl or phenyl; and R 10 " represents C 1 -C 7 alkyl or phenyl-C 1 -C 7 alkyl, and pharmaceutically acceptable salts thereof.
Claim 12
Dependent Claim
70 words
A compound as claimed in Claim 10 having the following general Formula 11:- wherein:- X 1 represents ethynyl or mono-, di- or trifluoromethyl; R" represents R 1 represents hydrogen, C 1 -C 4 alkyl or phenyl-C 1 -C 4 alkyl, R 13 represents C 1 -C 7 alkyl or phenyl, and R 14 represents benzyl or sec.butyl (i.e. -CH(CH 3 )CH 2 CH 3 ) and pharmaceutically acceptable salts thereof.
Claim 13
Dependent Claim
31 words
A pharmaceutical composition comprising a compound as claimed in any one of the preceding Claims as an active ingredient in admixture or otherwise associated with a pharmaceutically acceptable diluent or carrier.
Claim 14
Dependent Claim
31 words
A compound as claimed in any one of Claims 1 to 11 for use in inhibiting angiotensin-converting enzyme, enkephalinase or, when R 1 represents hydrogen, delta-aminolevulinic acid dehydrase in a patient.
Claim 15
Dependent Claim
15 words
A compound of the following general Formula 21:- wherein A represents tert-butyl, dibenzyl or trityl.
Claim 16
Dependent Claim
15 words
A compound of the following general Formula 21:- wherein A represents tert-butyl, dibenzyl or trityl.
Claim 17
Dependent Claim
62 words
A compound of the following general Formula 36:- wherein:- X 1 represents ethynyl or mono-, di- or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl or phenyl-C 1 -C 7 alkyl, R 9 represents hydroxy, C 1 -C 7 alkoxy or amino, and R 10 represents hydrogen, C 1 -C 7 alkyl, phenyl-C 1 -C 7 alkyl, phenyl or p-methoxyphenyl.
Claim 18
Dependent Claim
62 words
A compound of the following general Formula 36:- wherein:- X 1 represents ethynyl or mono-, di- or trifluoromethyl; R 1 represents hydrogen, C 1 -C 7 alkyl or phenyl-C 1 -C 7 alkyl, R 9 represents hydroxy, C 1 -C 7 alkoxy or amino, and R 10 represents hydrogen, C 1 -C 7 alkyl, phenyl-C 1 -C 7 alkyl, phenyl or p-methoxyphenyl.
Claim 19
Dependent Claim
26 words
A pharmaceutical composition comprising a compound according to Claim 15 as an active ingredient in admixture or otherwise associated with a pharmaceutically acceptable diluent or carrier.
Claim 20
Dependent Claim
16 words
A compound as claimed in Claim 10 for use in inhibiting delta-aminolevulinic acid dehydrase'in a patient.
References Cited (Backward Citations)
No citation records indexed.
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