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Pyridyl aminothiazoles as potent Chk1 inhibitors: optimization of cellular activity

ISSN:0960-894X
2012年第22卷第7期
Dudkin VY,Wang C,Arrington KL,Fraley ME,Hartman GD,Stirdivant SM,Drakas RA,Rickert K,Walsh ES,Hamilton K,Buser CA,Hardwick J,Tao W,Beck SC,Mao X,Lobell RB,Sepp-Lorenzino L Vadim Y. Dudkin1, Cheng Wang1, Kenneth L. Arrington1, Mark E. Fraley1, George D. Hartman1, Steven M. Stirdivant2, Robert A. Drakas2, Keith Rickert2, Eileen S. Walsh2, Kelly Hamilton2, Carolyn A. Buser2, James Hardwick2, Weikang Tao2, Stephen C. Beck2, Xianzhi Mao2, Robert B. Lobell2, Laura Sepp-Lorenzino2


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.

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ISSN:0960-894X
2012年第22卷第7期

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