58955-28-5Relevant articles and documents
Discovery of (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol- 5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide, a potent and orally efficacious mGlu5 receptor negative allosteric modulator
Hao, Junliang,Dehlinger, Veronique,Fivush, Adam M.,Rudyk, Helene C.E.,Britton, Thomas C.,Hollinshead, Sean P.,Vokits, Benjamin P.,Clark, Barry P.,Henry, Steven S.,Massey, Steven M.,Peng, Langu,Dressman, Bruce A.,Heinz, Beverly A.,Roberts, Edda F.,Bracey-Walker, Mallorie R.,Swanson, Steven,Catlow, John T.,Love, Patrick L.,Tepool, Anita D.,Peters, Steven C.,Simmons, Rosa Maria A.,Iyengar, Smriti,McKinzie, David L.,Monn, James A.
, p. 1249 - 1252 (2013)
A novel series of selective negative allosteric modulators (NAMs) for metabotropic glutamate receptor 5 (mGlu5) was discovered from an isothiazole scaffold. One compound of this series, (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3- (2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide (24), demonstrated satisfactory pharmacokinetic properties and, following oral dosing in rats, produced dose-dependent and long-lasting mGlu5 receptor occupancy. Consistent with the hypothesis that blockade of mGlu5 receptors will produce analgesic effects in mammals, compound 24 produced a dose-dependent reduction in paw licking responses in the formalin model of persistent pain.