Synthesis and SAR of Analogs of the M1 Allosteric Agonist TBPB. Part II: Amides, Sulfonamides and Ureas--The Effect of Capping the Distal Basic Piperidine Nitrogen

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5443-7. doi: 10.1016/j.bmcl.2008.09.032. Epub 2008 Sep 11.

Abstract

This letter describes the further synthesis and SAR, developed through an iterative analog library approach, of analogs of the highly selective M1 allosteric agonist TBPB by deletion of the distal basic piperidine nitrogen by the formation of amides, sulfonamides and ureas. Despite the large change in basicity and topology, M1 selectivity was maintained.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Amides / chemistry*
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry*
  • Chemistry, Pharmaceutical / methods*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Models, Chemical
  • Nitrogen / chemistry*
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry*
  • Receptor, Muscarinic M1 / chemistry*
  • Receptor, Muscarinic M1 / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Urea / chemistry*

Substances

  • 1-(1'-(2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo(d)imidazol-2-(3H)-one
  • Amides
  • Benzimidazoles
  • Piperidines
  • Receptor, Muscarinic M1
  • Sulfonamides
  • piperidine
  • Urea
  • Nitrogen