POTENT, LOW-MOLECULAR-WEIGHT RENIN INHIBITORS CONTAINING A C-TERMINAL HETEROCYCLE - HYDROGEN-BONDING AT THE ACTIVE-SITE

A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol-based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly. © 1990, American Chemical Society. All rights reserved.