• Journal Article

Synthesis and evaluation of 1,2,4-methyltriazines as mGluR5 antagonists

Citation

Olson, J., Gichinga, M., Butala, E., Navarro, H., Gilmour, B., & Carroll, F. (2011). Synthesis and evaluation of 1,2,4-methyltriazines as mGluR5 antagonists. Organic and Biomolecular Chemistry, 9(11), 4276-4286. DOI: 10.1039/C0OB01190H

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