Discovery of IRL 3461: a novel and potent endothelin antagonist with balanced ETA/ETB affinity

Bioorg Med Chem Lett. 1998 Aug 18;8(16):2241-6. doi: 10.1016/s0960-894x(98)00387-4.

Abstract

IRL 3461, N-butanesulfonyl-[N-(3,5-dimethylbenzoyl)-N-methyl-3-[4-(5-+ ++isoxazolyl) -phenyl]-alanyl]-(L)-valineamide, a potent and bifunctional (ETA + ETB) [Ki(ETA) = 1.8 nM, Ki(ETB) = 1.2 nM] antagonist was discovered by structural modification of IRL 2500, an ETB selective antagonist. IRL 3461 was found to be stable on incubation with human, rat, mouse, and guinea pig plasmas.

MeSH terms

  • Animals
  • Biphenyl Compounds / blood
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry*
  • Biphenyl Compounds / pharmacokinetics
  • Dipeptides / blood
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry*
  • Dipeptides / pharmacokinetics
  • Drug Design
  • Endothelin Receptor Antagonists*
  • Guinea Pigs
  • Humans
  • Indicators and Reagents
  • Mice
  • Molecular Structure
  • Rats
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Structure-Activity Relationship

Substances

  • Biphenyl Compounds
  • Dipeptides
  • Endothelin Receptor Antagonists
  • IRL 2500
  • Indicators and Reagents
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • IRL 3461