Design and synthesis of novel 2,7-dialkyl substituted 5(S)-amino-4(S)-hydroxy-8-phenyl-octanecarboxamides as in vitro potent peptidomimetic inhibitors of human renin

Novel low-molecular weight transition-state peptidomimetic renin inhibitors characterized by an all-carbon 8-phenyl substituted octanecarboxamide skeleton have been discovered based on a topographical design approach. The in vitro most potent inhibitors 21, 25 and 26 incorporating a strong H-bond acceptor group linked to the benzyl spacer of the (P3-P1)-unit had IC50s in the low nanomolar range against human renin.