A new class of orally active glycol renin inhibitors containing phenyllactic acid at P3

We prepared a new series of renin inhibitors based on dipeptide glycols, replacing the P4-P3 subsites with an O-(N-morpholinocarbonyl)-3-L-phenyllactic acid residue. This modification proved bioisosteric with Boc-L-phenylalanine, giving rise to highly potent human renin inhibitors (1-5 nM), e.g., SC-46944 (IC50 = 5 nM). Moreover, this change produced compounds that are orally efficacious in reducing plasma renin activity in salt-depleted marmosets.