Synthesis and structure-activity relationships of 2-(1,4'-bipiperidin-1'-yl)thiazolopyridine as H3 receptor antagonists

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6176-80. doi: 10.1016/j.bmcl.2009.09.006. Epub 2009 Sep 6.

Abstract

A series of 2-(1,4'-bipiperidine-1'-yl)thiazolopyridines was synthesized and evaluated as a new lead of non-imidazole histamine H(3) receptor antagonists. Introduction of diversity at the 6-position of the pyridine ring was designed to enhance in vitro potency and decrease hERG activity. The structure-activity relationships for these new thiazolopyridine antagonists are discussed.

MeSH terms

  • Animals
  • Haplorhini
  • Histamine Antagonists / chemical synthesis
  • Histamine Antagonists / chemistry*
  • Histamine Antagonists / pharmacokinetics
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Microsomes, Liver / metabolism
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacokinetics
  • Rats
  • Receptors, Histamine H3 / chemistry*
  • Receptors, Histamine H3 / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Trans-Activators / metabolism
  • Transcriptional Regulator ERG

Substances

  • ERG protein, human
  • Histamine Antagonists
  • Pyridines
  • Receptors, Histamine H3
  • Recombinant Proteins
  • Trans-Activators
  • Transcriptional Regulator ERG