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

Autor:	Kristin Kelly, Christopher John Helal, Tate Bonnie Frances, Mavis Diane Adam, Zhijun Kang, Marcia F. Peterson, Thomas G. Gant, Christopher B. Cooper, Michael K. Ahlijanian, Stanley William Kupchinsky, John C. Lucas, Frank S. Menniti, Sanner Mark Allen
Rok vydání:	2004
Předmět:	Cyclin E Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Nerve Tissue Proteins Isobutyramide Pharmacology Biochemistry Structure-Activity Relationship chemistry.chemical_compound Aminothiazole Alzheimer Disease Drug Discovery CDC2-CDC28 Kinases Protein kinase A Molecular Biology Molecular Structure biology Kinase Cyclin-dependent kinase 5 Cyclin-Dependent Kinase 2 Organic Chemistry Cyclin-dependent kinase 2 Cyclin-Dependent Kinase 5 Amides Cyclin-Dependent Kinases Thiazoles nervous system chemistry Enzyme inhibitor biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 14:5521-5525
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2004.09.006
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1a7b171a8387e73aea99641b4e26b53 https://doi.org/10.1016/j.bmcl.2004.09.006 Zobrazit plný text záznamu Full Text from ScienceDirect