期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 15, 期 21, 页码 4731-4735出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2005.07.072
关键词
inhibitors of cell cycle progression; parallel synthesis; tubulin binding
A novel series of inhibitors of, cancer cell proliferation, selective against p21 cell cycle checkpoint-disrupted cells vs. cells with intact p21 checkpoint, were identified by high-throughput screening. Optimization of both ends of the lead molecule to improve potency, using parallel synthesis and iterative design, is described. The 2-(1,4-dibenzodioxane)-substituted derivative 14 was identified as a highly selective and potent agent displaying an IC50 of 91 nM in the p21-deficient cell line. (c) 2005 Elsevier Ltd. All rights reserved.
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