Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P,'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13-or 14membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14- membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 ( ...
