title: Synthesis and evaluation of 1,2,4-methyltriazines as mGluR5 antagonists.
abstract: In previous studies we showed that 3-(substituted phenylethynyl)-5-methyl[1,2,4]triazine analogues of MPEP were potent antagonists of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro efficacy assay. In the present study we report the synthesis and evaluation of six 3-(substituted biphenylethynyl)-5-methyl[1,2,4]triazines (5a-f), and five 3-(substituted phenoxyphenylethynyl)-5-methyltriazines (6a-e). Compound 2-(4-fluorophenyl-5-[2-(5-methyl[1,2,4]triazine-3-yl)ethynyl]benzonitrile (5f) with an IC(50) of 28.2 nM was the most potent analogue.
authors.affiliation: Center for Organic and Medicinal Chemistry, Research Triangle Institute, P. O. Box 12194, Research Triangle Park, Durham, North Carolina 27709, USA.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Olson
authors.forename: Moses G
authors.initials: MG
authors.lastname: Gichinga
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Butala
authors.forename: Hernan A
authors.initials: HA
authors.lastname: Navarro
authors.forename: Brian P
authors.initials: BP
authors.lastname: Gilmour
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D015394:Molecular Structure; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014227:Triazines