Anti-hypertensive agents

Claim 1

A new compound having the general formula R-A-S-Z wherein R is hydrogen, formul, acetyl, propanoyl, butanoyl, phenylacetyl, phenylpropanoyl, benzoyl, cyclopentanecarbonyl, tert-butyloxycarbonyl, cyclopentanecarbonyl-L-lysyl, pyro-L-glutamyl-L-lysyl, L-arginyl, L-lysyl or pyro-L-glutamyl; A is a divalent moiety derived from methionine, cysteine, arginine, ω-nitro-arginine, lysine, ornithine, aspartic acid, asparagine, glutamic acid, glutamine, homocystein, penicillamine, norluecine, serine, β-alanine, ethionine, homoserine, isoserine, norvaline, threonine, α-aminobutyric acid, α-aminoisobutyric acid, cyclohexanyl-alanine, O-phosphothreonine, S-ethylcysteine, vinyl glycine or an α-methyl derivative of any of valine, leucine, isoleucine, cysteine, methionine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine or arginine, wherein the β-amino group of the moiety derived from β-alanine or the α-amino group of the moiety derived from each other named amino acid is in amide linkage with R when R is acyl and such moiety forms a primary amine group with R when R is H and the carboxyl group of said moiety is in thioester linkage with S; S is a sulfur atom joined in thioester linkage to A; and Z is selected from the following: ##STR69## wherein (i) R 1 and R 1 ', are each hydrogen or halogen, and R 2 and R 3 are each hydrogen, lower alkyl or trifluoromethyl provided that only one of R 2 and R 3 may be trifluoromethyl and further provided that at least one of R 1 , R 1 ', R 2 and R 3 must be halogen or trifluoromethyl; (ii) R 23 is hydrogen or lower alkyl and (iii) m is 0 or 1; ##STR70## wherein (i) R 4 and R 5 are each hydrogen, lower alkyl or phenyl-lower alkylene; (ii) n is 1, 2 or 3; (iii) R 6 is hydrogen or hydroxy or when n is 2, R 6 may also be halogen and (iv) m and R 23 are as stated in II above; ##STR71## wherein (i) R 7 is hydrogen, lower alkanoyl or amino (imino)methyl; (ii) p is 0 or an integer of from 1 to 4; (iii) R 25 is hydrogen but when m is 1, p is 0, R 4 is hydrogen and R 7 is lower alkanoyl, R 25 may also be lower alkyl; (iv) R 8 is selected from hydrogen, lower alkyl and hydroxy lower alkylene and R 9 is selected from hydrogen, lower alkyl, phenyl, phenyl-lower alkylene, hydroxy-lower alkylene, hydroxy phenyl-lower alkylene, mercapto-lower alkylene, lower alkyl-thio-lower alkylene, imidazolyl-lower alkylene, indolyl-lower alkylene, carbamoyl-lower alkylene and carboxy-lower alkylene but R 8 and R 9 may together constitute a (CH 2 ) v bridge wherein v is 3 or 4, thus forming a 5 or 6-membered ring with the N and C to which R 8 and R 9 are respectively attached and in such instance when v is 3 one hydrogen of (CH 2 ) v may be replaced by OH or halogen and when v is 4, one such hydrogen may be replaced by OH; (v) m and R 23 are each as defined in II above, and (vi) R 4 is as defined in III above, provided further however, that m and p may not both be 0, ##STR72## wherein (i) R 10 is hydrogen or lower alkyl; (ii) R 11 is hydrogen, lower alkyl or lower alkanoyl; (iii) X is O or S; (iv) m and R 23 are as stated in II above, and (v) R 8 , R 9 and p are as stated in IV above. ##STR73## wherein (i) R 12 is selected from carboxy, lower alkoxycarbonyl, carbamoyl, N-substituted carbamoyl and cyano; (ii) m and R 23 are as stated in II above; and (iii) R 8 , R 9 and p are as stated in IV above. ##STR74## wherein (i) R 13 is hydrogen, lower alkyl or phenyl-lower alkylene: (ii) R 14 is selected from hydrogen, lower alkyl, phenyl-lower alkylene, hydroxy-lower alkylene, amino-lower alkylene, guanidino-lower alkylene, imidazolyl-lower alkylene, indolyl-lower alkylene, mercapto-lower alkylene, lower alkyl-thio-lower alkylene, carbamoyl-lower alkylene and carboxy-lower alkylene; (iii) R 4 and R 5 are each as stated in III above; and (iv) q is 0, 1 or 2; ##STR75## wherein (i) R 15 and R 16 are each hydrogen, lower alkyl, phenyl or phenyl-lower alkylene; (ii) r is 0, 1 or 2; (iii) s is 1, 2 or 3; (iv) R 17 is hydrogen, hydroxy or lower alkyl and when s is 2, R 17 may also be halogen; (v) R 24 is hydroxy, amino or lower alkoxy; ##STR76## wherein (i) R 18 is hydrogen or lower alkyl; (ii) R 19 and R 20 are each lower alkyl and may together constitute a (CH 2 ) w bridge wherein w is 4, to form a ring of 5-carbons with the carbon to which they are attached; (iii) R 21 is hydrogen or lower alkyl and may constitute with R 19 a (CH 2 ) x bridge wherein x is 3, to form a five-membered ring with the N and C to which they are respectively attached; ##STR77## wherein (i) R 22 is hydrogen or lower alkyl; (ii) t is 0 or 1; and (iii) R 26 is selected from ##STR78## wherein u is 0 or 1 and R 23 is as defined for formula II above. ##STR79## wherein (i) z is 2 or 3; (ii) R 10 is as stated in V above; and (iii) R 3 is as stated in II above.