Pyridyl aminothiazoles as potent Chk1 inhibitors: Optimization of cellular activity

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• 作者：Vadim Y. Dudkin^a ; ^{vadim_dudkin@merck.com} ; Cheng Wang^a ; Kenneth L. Arrington^a ; Mark E. Fraley^a ; George D. Hartman^a ; Steven M. Stirdivant^b ; Robert A. Drakas^b ; Keith Rickert^b ; Eileen S. Walsh^b ; Kelly Hamilton^b ; Carolyn A. Buser^b ; James Hardwick^b ; Weikang Tao^b ; Stephen C. Beck^b ; Xianzhi Mao^b ; Robert B. Lobell^b ; Laura Sepp-Lorenzino^b
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 April, 2012
• 年：2012
• 卷：22
• 期：7
• 页码：2613-2619
• 全文大小：1514 K

文摘

Translation of significant biochemical activity of pyridyl aminothiazole class of Chk1 inhibitors into functional CEA potency required analysis and adjustment of both physical properties and kinase selectivity profile of the series. The steps toward optimization of cellular potency included elimination of CDK7 activity, reduction of molecular weight and polar surface area and increase in lipophilicity of the molecules in the series.