Rational design of 7-arylquinolines as non-competitive metabotropic glutamate receptor subtype 5 antagonists

  • Bioorg Med Chem Lett. 2007 Aug 15;17(16):4415-8. doi: 10.1016/j.bmcl.2007.06.030.
Jared B J Milbank  1 ,  Christopher S Knauer ,  Corinne E Augelli-Szafran ,  Annette T Sakkab-Tan ,  Kristin K Lin ,  Koji Yamagata ,  Jennifer K Hoffman ,  Nian Zhuang ,  John Thomas ,  Paul Galatsis ,  John A Wendt ,  John W Mickelson ,  Roy D Schwarz ,  Jack J Kinsora ,  Susan M Lotarski ,  Korana Stakich ,  Kristen K Gillespie ,  Wing W Lam ,  Abdul E Mutlib
Affiliations
  • 1. Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. [email protected]
PMID: 17590335 DOI: 10.1016/j.bmcl.2007.06.030
Abstract

Rational replacement of the alkyne linker of mGluR5 Antagonist MPEP gave 7-arylquinolines. SAR optimization gave an orally active compound with high affinity for the MPEP binding site.