4-Amino-2-(aryl)-butylbenzamides and Their conformationally constrained analogues. Potent antagonists of the human neurokinin-2 (NK(2)) receptor

Bioorg Med Chem Lett. 2003 Jul 7;13(13):2211-5. doi: 10.1016/s0960-894x(03)00343-3.

Abstract

A library, evaluating a range of piperazines, piperidines and acyclic amines, as replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue (2a) which was further optimised using classical single-compound synthesis to yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained analogues of (2j), generally offered no potency advantage in this particular series.

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology*
  • CHO Cells
  • Cricetinae
  • Cyclization
  • Drug Design
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Humans
  • In Vitro Techniques
  • Molecular Conformation
  • Peptide Library
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Rats
  • Receptors, Neurokinin-2 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Peptide Library
  • Piperidines
  • Receptors, Neurokinin-2