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

  • Biochem Biophys Res Commun. 1989 Apr 14;160(1):1-5. doi: 10.1016/0006-291x(89)91611-2.
G J Hanson  1 ,  J S Baran ,  H S Lowrie ,  M A Russell ,  S J Sarussi ,  K Williams ,  M Babler ,  S E Bittner ,  S E Papaioannou ,  P C Yang
Affiliations
  • 1. G.D. Searle and Co. Skokie, Ill. 60077.
PMID: 2496685 DOI: 10.1016/0006-291x(89)91611-2
Abstract

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.

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