Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

…, BP Nutley, FI Raynaud, P Sheldrake, M Walton…

文献索引：Wilson, Stuart C.; Atrash, Butrus; Barlow, Clare; Eccles, Susan; Fischer, Peter M.; Hayes, Angela; Kelland, Lloyd; Jackson, Wayne; Jarman, Michael; Mirza, Amin; Moreno, Javier; Nutley, Bernard P.; Raynaud, Florence I.; Sheldrake, Peter; Walton, Mike; Westwood, Robert; Whittaker, Steven; Workman, Paul; McDonald, Edward Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 22 p. 6949 - 6965

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被引用次数: 19

摘要

The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound αSβR- 21 inhibits CDK2/cyclin E with IC50= 30nM, CDK7-cyclin H with IC50= 1.3 μM, and CDK9- ...