- Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer's disease.
Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer's disease.
Bioorganic & medicinal chemistry letters (2004-10-16)
Christopher J Helal, Mark A Sanner, Christopher B Cooper, Thomas Gant, Mavis Adam, John C Lucas, Zhijun Kang, Stanley Kupchinsky, Michael K Ahlijanian, Bonnie Tate, Frank S Menniti, Kristin Kelly, Marcia Peterson
PMID15482916
摘要
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 (IC(50)=ca. 320nM). 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.
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