Synthesis and biological characterization of a series of novel diaryl amide M₁ antagonists

Bioorg Med Chem Lett. 2012 Nov 15;22(22):6923-8. doi: 10.1016/j.bmcl.2012.09.011. Epub 2012 Sep 23.

Abstract

Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M(1) acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M(1) antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement experiments demonstrated the competitive, orthosteric binding of these compounds; human selectivity data are presented.

MeSH terms

  • Acetylcholine / metabolism
  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Receptor, Muscarinic M1 / antagonists & inhibitors*
  • Receptor, Muscarinic M1 / genetics
  • Receptor, Muscarinic M1 / metabolism
  • Stereoisomerism
  • Stilbenes / chemical synthesis*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology
  • Structure-Activity Relationship

Substances

  • Amides
  • Piperazines
  • Receptor, Muscarinic M1
  • Stilbenes
  • VU0431263
  • VU0433670
  • Acetylcholine