Anti-hypertensive agents

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, .omega.-nitro-arginine, lysine, ornithine, aspartic acid, asparagine, glutamic acid, glutamine, homocystein, penicillamine, norluecine, serine, .beta.-alanine, ethionine, homoserine, isoserine, norvaline, threonine, .alpha.-aminobutyric acid, .alpha.-aminoisobutyric acid, cyclohexanyl-alanine, O-phosphothreonine, S-ethylcysteine, vinyl glycine or an .alpha.-methyl derivative of any of valine, leucine, isoleucine, cysteine, methionine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine or arginine, wherein the .beta.-amino group of the moiety derived from .beta.-alanine or the .alpha.-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.sub.1 and R.sub.1 ', are each hydrogen or halogen, and R.sub.2 and R.sub.3 are each hydrogen, lower alkyl or trifluoromethyl provided that only one of R.sub.2 and R.sub.3 may be trifluoromethyl and further provided that at least one of R.sub.1, R.sub.1 ', R.sub.2 and R.sub.3 must be halogen or trifluoromethyl;
• (ii) R.sub.23 is hydrogen or lower alkyl and
• (iii) m is 0 or 1;
• ##STR70## wherein (i) R.sub.4 and R.sub.5 are each hydrogen, lower alkyl or phenyl-lower alkylene;
• (ii) n is 1, 2 or 3;
• (iii) R.sub.6 is hydrogen or hydroxy or when n is 2, R.sub.6 may also be halogen and
• (iv) m and R.sub.23 are as stated in II above;
• ##STR71## wherein (i) R.sub.7 is hydrogen, lower alkanoyl or amino (imino)methyl;
• (ii) p is 0 or an integer of from 1 to 4;
• (iii) R.sub.25 is hydrogen but when m is 1, p is 0, R.sub.4 is hydrogen and R.sub.7 is lower alkanoyl, R.sub.25 may also be lower alkyl;
• (iv) R.sub.8 is selected from hydrogen, lower alkyl and hydroxy lower alkylene and R.sub.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.sub.8 and R.sub.9 may together constitute a (CH.sub.2).sub.v bridge wherein v is 3 or 4, thus forming a 5 or 6-membered ring with the N and C to which R.sub.8 and R.sub.9 are respectively attached and in such instance when v is 3 one hydrogen of (CH.sub.2).sub.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.sub.23 are each as defined in II above, and
• (vi) R.sub.4 is as defined in III above, provided further however, that m and p may not both be 0, ##STR72## wherein (i) R.sub.10 is hydrogen or lower alkyl;
• (ii) R.sub.11 is hydrogen, lower alkyl or lower alkanoyl;
• (iii) X is O or S;
• (iv) m and R.sub.23 are as stated in II above, and
• (v) R.sub.8, R.sub.9 and p are as stated in IV above. ##STR73## wherein (i) R.sub.12 is selected from carboxy, lower alkoxycarbonyl, carbamoyl, N-substituted carbamoyl and cyano;
• (ii) m and R.sub.23 are as stated in II above;
• and
• (iii) R.sub.8, R.sub.9 and p are as stated in IV above. ##STR74## wherein (i) R.sub.13 is hydrogen, lower alkyl or phenyl-lower alkylene:
• (ii) R.sub.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.sub.4 and R.sub.5 are each as stated in III above;
• and
• (iv) q is 0, 1 or 2;
• ##STR75## wherein (i) R.sub.15 and R.sub.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.sub.17 is hydrogen, hydroxy or lower alkyl and when s is 2, R.sub.17 may also be halogen;
• (v) R.sub.24 is hydroxy, amino or lower alkoxy;
• ##STR76## wherein (i) R.sub.18 is hydrogen or lower alkyl;
• (ii) R.sub.19 and R.sub.20 are each lower alkyl and may together constitute a (CH.sub.2).sub.w bridge wherein w is 4, to form a ring of 5-carbons with the carbon to which they are attached;
• (iii) R.sub.21 is hydrogen or lower alkyl and may constitute with R.sub.19 a (CH.sub.2).sub.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.sub.22 is hydrogen or lower alkyl;
• (ii) t is 0 or 1;
• and
• (iii) R.sub.26 is selected from ##STR78## wherein u is 0 or 1 and R.sub.23 is as defined for formula II above. ##STR79## wherein (i) z is 2 or 3;
• (ii) R.sub.10 is as stated in V above;
• and
• (iii) R.sub.3 is as stated in II above.