Kinesin spindle protein (KSP) inhibitors. Part 6: Design and synthesis of 3,5-diaryl-4,5-dihydropyrazole amides as potent inhibitors of the mitotic kinesin KSP

被引：28

作者：

Coleman, Paul J.

Schreler, John D.

Cox, Christopher D.

Fraley, Mark E.

Garbaccio, Robert M.

Buser, Carolyn A.

Walsh, Eileen S.

Hamilton, Kelly

Lobell, Robert B.

Rickert, Keith

Tao, Weikang

Diehl, Ronald E.

South, Vicki J.

Davide, Joseph P.

Kohl, Nancy E.

Yan, Youwei

Kuo, Lawrence

Prueksaritanont, Thomayant

Li, Chunze

Mahan, Elizabeth A.

Fernandez-Metzler, Carmen

Salata, Joseph J.

Hartman, George D.

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Canc Res, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Biol Struct, West Point, PA 19486 USA

[4] Merck Res Labs, Dept Drug Metab, West Point, PA 19486 USA

[5] Merck Res Labs, Dept Cellular Safety, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 19期

关键词：

cancer; kinesin spindle protein; KSP inhibitors; antimitotics; dihydropyrazoles; p-glycoprotein;

D O I：

10.1016/j.bmcl.2007.07.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3,5-Diaryl-4,5-dihydropyrazoles were discovered to be potent KSP inhibitors with excellent in vivo potency. These enzyme inhibitors possess desirable physical properties that can be readily modified by incorporation of a weakly basic amine. Careful adjustment of amine basicity was essential for preserving cellular potency in a multidrug resistant cell line while maintaining good aqueous solubility. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5390 / 5395

页数：6

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