Synthesis, modelling and NK1 antagonist evaluation of a non-rigid cyclopropane-containing analogue of CP-99,994

Bioorg Med Chem Lett. 2001 Mar 12;11(5):659-61. doi: 10.1016/s0960-894x(01)00020-8.

Abstract

A non-rigid cyclopropane-containing diamine analogue of CP-99,994 was synthesised and was found to have only moderate NK1 receptor binding affinity. Molecular dynamics calculations of the conformational space of the former compound gave good correlation between observed activity and a recently published pharmacophore model, lending predictive value to the latter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Neurokinin-1 Receptor Antagonists*
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / metabolism
  • Piperidines / pharmacology
  • Receptors, Neurokinin-1 / chemistry
  • Receptors, Neurokinin-1 / metabolism
  • Stereoisomerism

Substances

  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Receptors, Neurokinin-1
  • 3-(2-methoxybenzylamino)-2-phenylpiperidine