Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors

…, WH Parsons, WJ Greenlee, AA Patchett

Index: Weber; Halgren; Doyle; Lynch; Siegl; Parsons; Greenlee; Patchett Journal of Medicinal Chemistry, 1991 , vol. 34, # 9 p. 2692 - 2701

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Citation Number: 43

Abstract

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 ( ...