Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1362-5. doi: 10.1016/j.bmcl.2005.11.047. Epub 2005 Dec 5.

Abstract

The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1)) receptor antagonists is described. The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration.

MeSH terms

  • Administration, Oral
  • Amines / chemistry
  • Animals
  • CHO Cells
  • Cricetinae
  • Cross-Linking Reagents / chemistry
  • Drug Design*
  • Humans
  • Molecular Structure
  • Neurokinin-1 Receptor Antagonists*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Pyrimidines / chemistry
  • Receptors, Neurokinin-1 / metabolism
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Amines
  • Cross-Linking Reagents
  • Neurokinin-1 Receptor Antagonists
  • Pyridines
  • Pyrimidines
  • Receptors, Neurokinin-1
  • netupitant
  • befetupitant