Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity

Bioorg Med Chem Lett. 2013 Nov 1;23(21):6004-9. doi: 10.1016/j.bmcl.2013.08.013. Epub 2013 Aug 19.

Abstract

A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor antagonists has been discovered. Compound 17 was identified as a centrally penetrant molecule with high receptor occupancy which demonstrates robust oral activity in rodent models of obesity. In addition compound 17 possesses clean CYP and hERG profiles and shows no behavioral changes in the Irwin test.

Keywords: H3 antagonists; Histamine.

MeSH terms

  • Animals
  • Histamine H3 Antagonists / chemistry*
  • Histamine H3 Antagonists / metabolism
  • Histamine H3 Antagonists / pharmacokinetics
  • Histamine H3 Antagonists / therapeutic use*
  • Humans
  • Microsomes, Liver / metabolism
  • Obesity / drug therapy*
  • Rats
  • Receptors, Histamine H3 / metabolism

Substances

  • Histamine H3 Antagonists
  • Receptors, Histamine H3