Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists

  • Bioorg Med Chem Lett. 2006 Jul 1;16(13):3371-5. doi: 10.1016/j.bmcl.2006.04.032.
Santosh S Kulkarni  1 ,  Barbara Nightingale ,  Christina M Dersch ,  Richard B Rothman ,  Amy Hauck Newman
Affiliations
  • 1. Medicinal Chemistry Section, National Institute on Drug Abuse, Intramural Research Program, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
PMID: 16678408 DOI: 10.1016/j.bmcl.2006.04.032
Abstract

A series of diaryl amides was designed and synthesized as novel nonethynyl mGluR5 antagonists. The systematic variation of the pharmacophoric groups led to the identification of a lead compound that demonstrated micromolar affinity for the mGluR5. Further optimization resulted in compounds with improved binding affinities and antagonist profiles, in vitro.