Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists

Bioorg Med Chem Lett. 2007 Apr 1;17(7):2074-9. doi: 10.1016/j.bmcl.2006.12.083. Epub 2007 Jan 4.

Abstract

A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolinamide, exhibited nanomolar affinity at the mGluR5 and will serve as a template for future drug design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry*
  • Animals
  • Binding Sites
  • CHO Cells
  • Chemistry, Pharmaceutical / methods*
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Mice
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Substance-Related Disorders / drug therapy

Substances

  • Amides
  • Grm5 protein, mouse
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate