Author/Authors :
Christopher J. Helal، نويسنده , , Mark A. Sanner، نويسنده , , Christopher B. Cooper، نويسنده , , Thomas Gant، نويسنده , , Mavis Adam، نويسنده , , John C. Lucas، نويسنده , , Zhijun Kang، نويسنده , , Stanley Kupchinsky، نويسنده , , Michael K. Ahlijanian، نويسنده , , Bonnie Tate، نويسنده , , Frank S. Menniti، نويسنده , , Kristin Kelly، نويسنده , , Marcia Peterson، نويسنده ,
Abstract :
High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC50 = ca. 320 nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved.
Keywords :
fax: +1 860 6865291 , e-mail: chris_j_helal@groton.pfizer.com , 2-Aminothiazole , Cyclin-dependent kinase 5 , p25 , Cyclindependentkinase 2 , Cyclin E , Alzheimer s disease.* Corresponding author. Tel.: +1 860 715 5064
