The P1N-isopropyl motif bearing hydroxyethylene dipeptide isostere analogues of aliskiren are in vitro potent inhibitors of the human aspartyl protease renin

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4863-7. doi: 10.1016/j.bmcl.2009.05.128. Epub 2009 Jun 26.

Abstract

Novel nonpeptide small molecule renin inhibitors bearing an N-isopropyl P(1) motif were designed based on initial lead structures 1 and aliskiren (2). (P(3)-P(1))-Benzamide derivatives such as 9a and 34, as well as the corresponding P(1) basic tertiary amine derivatives 10 and 35 were found to display low nanomolar inhibition against human renin in vitro.

MeSH terms

  • Administration, Oral
  • Amides / chemistry*
  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / chemistry*
  • Antihypertensive Agents / pharmacology
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology
  • Callithrix
  • Ethylenes / chemistry*
  • Fumarates / chemistry*
  • Humans
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Renin / antagonists & inhibitors*
  • Renin / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Antihypertensive Agents
  • Benzamides
  • Ethylenes
  • Fumarates
  • Protease Inhibitors
  • aliskiren
  • hydroxyethylene
  • Renin