1382452-20-1Relevant academic research and scientific papers
Discovery of (R)-(2-fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-hydroxypiperidin-1-yl)methanone (ML337), an mGlu3 selective and CNS penetrant negative allosteric modulator (NAM)
Wenthur, Cody J.,Morrison, Ryan,Felts, Andrew S.,Smith, Katrina A.,Engers, Julie L.,Byers, Frank W.,Daniels, J. Scott,Emmitte, Kyle A.,Conn, P. Jeffrey,Lindsley, Craig W.
, p. 5208 - 5212 (2013/07/26)
A multidimensional, iterative parallel synthesis effort identified a series of highly selective mGlu3 NAMs with submicromolar potency and good CNS penetration. Of these, ML337 resulted (mGlu3 IC50 = 593 nM, mGlu2 IC50 >30 μM) with B:P ratios of 0.92 (mouse) to 0.3 (rat). DMPK profiling and shallow SAR led to the incorporation of deuterium atoms to address a metabolic soft spot, which subsequently lowered both in vitro and in vivo clearance by >50%.
