Anti-hypertensive agents

Claim 1

A new compound having the general formula R--A--S--Z wherein, R is hydrogen, formyl, 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 phenylglycine, β-benzyl aspartic acid, γ-benzyl glutamic acid, S-benzyl cysteine, O-benzyl aspartic acid, O-benzyl tyrosine, O-benzyl threonine, β-phenyl serine, thyronine, β-2-thienylserine, β-2-thienylalanine, α-methyl histidine, α-methyl tyrosine, α-methyl phenylalanine, α-methyl tryptophan, substituted tyrosine wherein the substituent is halo, nitro, methoxy or hydroxy, or substituted phenylaline wherein the substituent is selected from nitro, amino and methoxy or substituted tryptophan wherein the substituent is selected from methyl and methoxy, the α-amino group of which moiety is in amide linkage with R when R is acyl, and forms a primary amino group with R when R is H, and the carboxyl group of which 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 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 whcn 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 0 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 each 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 23 is as stated in II. above.