Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists

Bioorg Med Chem. 2006 May 15;14(10):3285-99. doi: 10.1016/j.bmc.2005.12.046. Epub 2006 Jan 26.

Abstract

Melanin concentrating hormone (MCH) receptor antagonists have been proposed as potential treatments of obesity. MCH receptor antagonists with a biphenylamine subunit have been reported previously at Schering-Plough. Herein, we report the discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of the biphenylamine moiety in order to eliminate its potential mutagenic liability. Structure-activity relationships in this series were found to be very similar to those of the original biphenylamine series, suggesting that the two series have similar binding modes.

MeSH terms

  • Aminobiphenyl Compounds / chemistry*
  • Animals
  • Bridged Bicyclo Compounds / chemistry*
  • Cell Line
  • Cricetinae
  • Drug Evaluation, Preclinical
  • Heptanes / chemistry*
  • Heptanes / pharmacology
  • Mice
  • Molecular Structure
  • Mutagens / chemistry
  • Rats
  • Receptors, Pituitary Hormone / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Aminobiphenyl Compounds
  • Bridged Bicyclo Compounds
  • Heptanes
  • Mutagens
  • Receptors, Pituitary Hormone
  • melanin-concentrating hormone receptor