Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer's disease.

Helal CJ, Sanner MA, Cooper CB, Gant T, Adam M, Lucas JC, Kang Z, Kupchinsky S, Ahlijanian MK, Tate B, Menniti FS, Kelly K, Peterson M

Neuroscience Medicinal Chemistry and Pharmacology, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. chris_j_helal@groton.pfizer.com

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.

Published 14 October 2004 in Bioorg Med Chem Lett, 14(22): 5521-5.
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