Lucas-Hourani, Marianne published the artcileOriginal 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH), Name: 2-Chloro-5-(trifluoromethyl)pyrazine, the main research area is alkoxypyrazolylazine preparation inhibitor human dihydroorotate dehydrogenase SAR.
Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogs. As in our previous report, the structure-activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biol. evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine (I). Inhibition of DHODH by this compoundI was confirmed in an array of in vitro assays, including enzymic tests and cell-based assays for viral replication and cellular growth. I was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.
Journal of Medicinal Chemistry published new progress about Antiviral agents. 799557-87-2 belongs to class pyrazines, name is 2-Chloro-5-(trifluoromethyl)pyrazine, and the molecular formula is C5H2ClF3N2, Name: 2-Chloro-5-(trifluoromethyl)pyrazine.