RENIN INHIBITING POLYHYDROXYMONOAMIDES

摘要

Disclosed herein are compounds of the formula: R1CH2CH(X)CH(Y)CH(Z)CHR2C(O)NHCHR3CH(OH)CH(OH)R4 wherein R1 is a terminal unit, for example lower cycloalkyl or phenyl; R2 is, for example, an optionally substituted alkyl, cycloalkylmethyl, benzyl, 4-imidazolylmethyl, 2-thienylmethyl or 4thiazolylmethyl; R3 is alkyl, cycloalkylmethyl or an optionally substituted benzyl; R4 is alkyl or cycloalkyl; and X and Y each is hydroxy and Z is hydrogen, or X and Z each is hydroxy and Y is hydrogen; with the provisos that (a) the carbon atom bearing R2 has the "R" configuration except when R2 is 2-thienylmethyl or 2-thiazolylmethyl, X and Y each is hydroxy and Z is hydrogen, then the carbon atom bearing R2 has the "S" configuration; (b) the carbon atoms bearing R3 and R4 each has the "S" configuration; and (c) the carbon atom located between the last-said two carbon atoms has the "R" configuration. The compounds inhibit renin activity and are indicated for the treatment of hypertension and congestive heart failure.