Renin-inhibitory peptide analogs

Claim 1

A compound having the formula: ##STR42## wherein: A is (i) ##STR43## where: A" is hydrogen or phenoxyacetyl; (ii) ##STR44## where: A"' is hydrogen; ##STR45## wherein n is 0-5; or ##STR46## where R 3' has the same meaning as set out further below or hydrogen; B' is absent; glycyl; or ##STR47## D' is absent; or ##STR48## where Z is (CH 2 ) n and n is 1 or 2; or --S--; R 1' or R 1" is hydrogen; C 1-4 alkyl; hydroxy C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2-3 alkyl; or methylthiomethyl; R 2' is hydrogen; C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; or indolyl; and R 3' is C 3-6 alkyl; C 3-7 cycloalkyl; phenyl; or phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; (iii) ##STR49## where: A"" is hydrogen; or ##STR50## wherein: X"" is ##STR51## and R a 2" and R b 2" are independently hydrogen; Y'--(CH 2 ) n -- or Y'--(CH 2 ) m --CH═CH--(CH 2 ) p' where Y' is hydrogen; aryl; aryl substituted with up to five members independently selected from the group consisting of C 1-8 alkyl, trifluoromethyl, hydroxy, C 1-4 alkoxy, and halo; n is 0 to 5; m is 0 to 2; and p is 0 to 2; except that where X"" is --O--, only one of R a 2" or R b 2" is present; and R 1" is hydrogen; C 1-4 alkyl, provided, that where R 1 is i-propyl, and B is Phe or Tyr, A is other than hydrogen or phenoxyacetyl; hydroxy C 1-4 alkyl; aryl; aryl substituted with up to three members selected from the group consisting of C 1-4 alkyl, trifluoromethyl, hydroxy, C 1-4 alkoxy; fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2-3 alkyl; or methylthiomethyl; X--Y is ##STR52## wherein Z' is H, CH 3 , (CH 2 ) n B", (CH 2 ) n C" wherein n is 0-4, or ##STR53## wherein R a is C 1 -C 6 alkyl, ar-C 1-6 -alkyl, C 3-7 cycloalkyl; C 1-6 alkoxy; aryl or heteroaryl; R 1 is C 1 -C 4 branched or linear alkyl, C 3 -C 6 cycloalkyl, phenyl or monosubstituted phenyl where the substituent is OH, Cl, Br, F, CH 3 , CF 3 , I or OCH 3 ; R 2 is hydrogen or ##STR54## wherein R a 5 and R b 5 are independently selected from hydrogen, C 1 -C 4 alkyl, hydroxy or C 3 -C 7 cycloalkyl; B" is ##STR55## C" is NH 2 , NHCH 2 R 3" , --NH-- or ##STR56## wherein R 3" is C 3 -C 6 alkyl, C 3 -C 7 cycloalkyl, phenyl or mono-substituted phenyl wherein the substituent is methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo or iodo; and B--C is ##STR57## wherein R 6 is selected from: (a) OR; NHR; or NR 2 , where each R is independently hydrogen or C 1-4 alkyl; (b) B""--E wherein B"" is absent; glycyl; ##STR58## wherein n is 1 or 2; or --S--; R 1'" is hydrogen; C 1-4 alkyl; hydroxy C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2-3 alkyl; or methylthiomethyl; and E is OR; NHR, or N(R) 2 , where each R is independently hydrogen or C 1-4 alkyl; and (c) B°--D--E wherein B° is --Y--(CH 2 ) n --R 6a (1) where Y is --NH-- or --O--; n is 0 to 5; and R 6a is hydrogen, hydroxy; C 1-4 alkyl; C 3-7 cycloalkyl; aryl; aryl substituted with up to five members independently selected from the group consisting of C 1-6 alkyl, trifluoromethyl, hydroxy, C 1-4 alkoxy, amino, mono- or di-C 1-4 alkylamino, and halo; amino; mono-, di-, or tri-C 1-4 alkylamino; guanidyl; heterocyclic; or heterocyclic substituted with up to five members independently selected from the group consisting of C 1-6 alkyl, hydroxy, trifluoromethyl, C 1-4 alkoxy, halo, aryl, aryl C 1-4 alkyl, amino, and mono- or di-C 1-4 alkylamino; ##STR59## where Y is as defined above; n is 0 or 1; k is 0 or 1; q is 1 to 4; m is 1 to 4. and R b 6 and R a 6 are each independently the same as R 6a above and R a 6 may additionally be ##STR60## where R 7 is hydrogen or C 1-3 alkyl; ##STR61## where Y is as defined above; n is 0 or 1; and Z is ##STR62## where n is 0 or 1; and R 7 is as defined above; or ##STR63## where n is 0 or 1; or ##STR64## where R 1 is as defined above; D is absent; glycyl; sarcosyl; or ##STR65## and E is absent; OR; NHR; or N(R) 2' where R is independently hydrogen or C 1-4 alkyl; (d) --Y--(CH 2 ) n --R a 6 where Y is --NH-- or --O--; n is 0 to 5; and R a 6 is hydrogen; C 1-3 alkyl; C 3-7 cycloalkyl; naphthyl; phenyl; phenyl substituted with up to five members independently selected from the group consisting of methyl, trifluoromethyl, hydroxyl, methoxy, amino, fluoro, chloro, bromo, and iodo; imidazolyl; pyridyl; pyrryl; hydroxyl; amino; C 1-4 alkyl mono-, di-, or tri-substituted amino; guanidyl; piperidyl; tetrahydropyrryl; or N-substituted piperidyl or tetrahydropyrryl where the N-substituent is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, phenyl, benzyl, naphthyl, and naphthylmethyl; (e) ##STR66## where Y is as defined above; n is 0 or 1; k is 0 or 1; q is 1 to 4; m is 1 to 4; and R b 6 and R a 6 are each independently the same as R 6a above; or (f) ##STR67## where Y is as defined above; n is 0 or 1; and Z is ##STR68## where n is 0 or 1; and R 7 is hydrogen or C 1-3 alkyl; or ##STR69## where n is 0 or 1; and pharmaceutically acceptable salts thereof.