title: Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists.
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.
authors.affiliation: Medicinal Chemistry Section, National Institute on Drug Abuse, Intramural Research Program, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Santosh S
authors.initials: SS
authors.lastname: Kulkarni
authors.forename: Amy Hauck
authors.initials: AH
authors.lastname: Newman
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D000577:Amides; C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate