Design and discovery of new (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides as potent renin inhibitors

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7677-82. doi: 10.1016/j.bmcl.2012.09.103. Epub 2012 Oct 17.

Abstract

Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemical synthesis
  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Haplorhini
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Renin / antagonists & inhibitors*
  • Renin / blood
  • Renin / metabolism
  • Structure-Activity Relationship

Substances

  • (3S,5R)-5-(4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl)piperidine-3-carboxamide
  • Angiotensin-Converting Enzyme Inhibitors
  • Piperazines
  • Piperidines
  • Renin