| abstract |
PURPOSE: To prohibit the angiotensinogen cleavage action of proteolytic enzyme useful for the treatment of a renin-associated hypertension, hyperaldosteronism, and congestive heart failure. n CONSTITUTION: The compd. of formula I [A is H, an aryl, etc.; B, D are formulas II, III (R 13 is H, a 1 to 5C alkyl, etc.; R 10 is aryl, substd. 1 to 5C alkyl, etc.); R 1 is H, a 3 to 7C cycloalkyl, etc.; R 2 is H, phenyl, etc.; X is CH 2 , O, etc.; R 3 is H, CO 2 H, etc.; R 4 is H, etc., when X is O, etc.; amino acid, etc., when X is CH 2 , etc.;] and its salt. The compd. is obtd. by enolizing the bicyclic lactam deriv. of formula IV by using LDA and a base, then adding the enolide to nitrogen protection α-aminoaldehyde to obtain a protected aminoalcohol deriv. and removing the nitrogen protecting group of the deriv., then coupling the deriv. to the carboxylic acids of the formula A, B and D by a standard peptide method and finally subjecting the product to deprotection. n COPYRIGHT: (C)1992,JPO |