New Renin Inhibitors Containing Pseudodipeptidic Units in P₃–P₂ and P₁–P₁′ Positions

抄録

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.