New renin inhibitors containing pseudodipeptidic units in P 3-P2 and P1-P1′ positions

Abstract

A series of four non-peptidic renin inhibitors have been designed and synthesized. All of them contain in their molecule (3S,4S)-4-amino-5-cyclohexyl- 3-hydroxypentanoic acid (ACHPA), a hydrophobic portion at the C-terminus and a second dipeptide-like transition state analog or unnatural dipeptidic fragment at the N-terminus. Inhibitory activity of the compounds was measured in vitro by high performance liquid chromatography (HPLC). Their IC50 (M/l) values were: <10-3 (12), 1.0×10-6 (19), 4.0×10-4 (23) and 1.0×10-6 (29), respectively. All the compounds are stable against chymotrypsin. © 2005 Pharmaceutical Society of Japan.