Anti-hypertensive agents

Claim 1

A new compound having the general formula I. R--A--S--Z, and the physiologically acceptable salts thereof, wherein: R is selected from hydrogen, formyl, acetyl, propanoyl, butanoyl, phenylacetyl, phenylpropanoyl, benzoyl, cyclopentanecarbonyl, tert-butyloxycarbonyl, cyclopentanecarbonylL-lysyl, pyro-L-glutamyl-L-lysyl, L-arginyl, L-lysyl and pyro-L-glutamyl, A is selected from phenylalanyl, glycyl, alanyl, tryptophyl, tyrosyl, isoleucyl, leucyl, histidyl and valyl and the -amino group of A is in amide linkage with R when R is an acyl group and forms a primary amino group with R when R is hydrogen; S is a sulfur atom joined to A in a thioester linkage; and Z is selected from the following: ##STR60## 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; ##STR61## 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; ##STR62## 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 when R 9 is selected from hydrogen, lower alkyl, phenyl, phenyl-lower alkylene, hydroxy-lower alkylene, hydroxyphenyl-lower alkylene, amino-lower alkylene, guanidino-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 (iv) R 4 is as defined in III. above, provided further, however, that m and p may not both be 0. ##STR63## 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; ##STR64## 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; ##STR65## 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 as stated in III. above; and (iv) q is 0, 1 or 2 ##STR66## 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; and (v) R 24 is hydroxy, amino or lower alkoxy; provided that when R 24 is OH, s is 2, and R 17 is H or OH: (a) if r is 0, R 16 may not be methyl or H, and (b) if r is 1, R 15 and R 16 may not both be H and R 16 may not be methyl if R 15 is H ##STR67## 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; provided, however, that when R 19 and R 21 constitute (CH 2 ) x , R 18 may not be hydrogen or methyl ##STR68## wherein (i) R 22 is hydrogen or lower alkyl; (ii) t and u are each 0 or 1; (iii) R 23 is as stated in II. above; provided, however, that u may not be zero when R 23 is H; and ##STR69## 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.