2. Academic Validation
  3. Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors

Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors

  • Bioorg Med Chem Lett. 2004 Mar 22;14(6):1483-6. doi: 10.1016/j.bmcl.2004.01.012.
John Wityak 1,  Frank W Hobbs,  Daniel S Gardner,  Joseph B Santella 3rd,  Joseph J Petraitis,  Jung-Hui Sun,  Margaret F Favata,  Andrea J Daulerio,  Kurumi Y Horiuchi,  Robert A Copeland,  Peggy A Scherle,  Bruce D Jaffe,  James M Trzaskos,  Ronald L Magolda,  George L Trainor,  John V Duncia
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Pharmaceuticals Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA.
PMID: 15006386 DOI: 10.1016/j.bmcl.2004.01.012
Abstract

Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK Inhibitor lead SH053 (IC(50)=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 ED(50)=5 mg/kg.

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