691405-00-2Relevant articles and documents
Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors
Wityak, John,Hobbs, Frank W.,Gardner, Daniel S.,Santella III, Joseph B.,Petraitis, Joseph J.,Sun, Jung-Hui,Favata, Margaret F.,Daulerio, Andrea J.,Horiuchi, Kurumi Y.,Copeland, Robert A.,Scherle, Peggy A.,Jaffe, Bruce D.,Trzaskos, James M.,Magolda, Ronald L.,Trainor, George L.,Duncia, John V.
, p. 1483 - 1486 (2007/10/03)
Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK inhibitor lead SH053 (IC50=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound 41, exhibiting a MEK IC 50=12 nM showed ip activity in a TPA-induced ear edema model with an ED50=5 mg/kg.
