Synthesis and Pharmacological Evaluation of Phenylethynyl[1,2,4]methyltriazines as Analogues of 3-Methyl-6-(phenylethynyl)pyridine
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- 作者：F. Ivy Carroll ; Sharadsrikar V. Kotturi ; Herná ; n A. Navarro ; S. Wayne Mascarella ; Brian P. Gilmour ; Forrest L. Smith ; Bichoy H. Gabra ; William L. Dewey
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：July 12, 2007
- 年：2007
- 卷：50
- 期：14
- 页码：3388 - 3391
- 全文大小：62K
- 年卷期：v.50,no.14(July 12, 2007)
- ISSN：1520-4804
文摘
Procedures were developed for the synthesis of 3-methyl-5-phenylethynyl[1,2,4]triazine (4), 6-methyl-3-phenylethynyl[1,2,4]triazine (5), and 5-methyl-3-phenylethynyl[1,2,4]triazine (6a) as analogues of 2-methyl-6-(phenylethynyl)pyridine (2). The compounds were evaluated for antagonism of glutamate-mediatedmobilization of internal calcium in an mGluR5 in vitro efficacy assay. The most potent of the three analogueswas 6a. Twenty additional analogues of 6a were synthesized and evaluated for mGluR5 antagonist efficacy.The most potent compounds were 3-(3-methylphenylethynyl)-5-methyl[1,2,4]triazine (6b), 5-(3-chlorophenylethynyl)-5-methyl[1,2,4]triazine (6c), and 3-(3-bromophenylethynyl)-5-methyl[1,2,4]triazine (6d).