Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5439-42. doi: 10.1016/j.bmcl.2008.09.023. Epub 2008 Sep 10.

Abstract

This Letter describes the first account of the synthesis and SAR, developed through an iterative analogue library approach, of analogues of the highly selective M1 allosteric agonist TBPB. With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / chemistry
  • Allosteric Regulation
  • Allosteric Site
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry*
  • Binding Sites
  • Chemistry, Pharmaceutical / methods*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Models, Chemical
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry*
  • Receptor, Muscarinic M1 / chemistry*
  • Receptor, Muscarinic M1 / metabolism
  • Structure-Activity Relationship
  • Time Factors

Substances

  • 1-(1'-(2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo(d)imidazol-2-(3H)-one
  • Benzimidazoles
  • Ligands
  • Piperidines
  • Receptor, Muscarinic M1
  • Acetylcholine