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Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors.
Bioorg Med Chem Lett
; 14(6): 1483-6, 2004 Mar 22.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15006386
RESUMEN
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.