Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP

被引：44

作者：

Roecker, Anthony J.

Coleman, Paul J.

Mercer, Swati P.

Schreier, John D.

Buser, Carolyn A.

Walsh, Eileen S.

Hamilton, Kelly

Lobell, Robert B.

Tao, Weikang

Diehl, Ronald E.

South, Vicki J.

Davide, Joseph P.

Kohl, Nancy E.

Yan, Youwei

Kuo, Lawrence C.

Li, Chunze

Fernandez-Metzler, Carmen

Mahan, Elizabeth A.

Prueksaritanont, Thomayant

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 20期

关键词：

KSP inhibitors; antimitotics; Pgp; kinesins; 1,4-diaryl-4,5-dihydropyrazoles; copper-mediated N-arylation; kinesin spindle protein; cancer;

D O I：

10.1016/j.bmcl.2007.07.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5677 / 5682

页数：6

共 17 条

[11] Kinesin spindle protein (KSP) inhibitors. Part 3: Synthesis and evaluation of phenolic 2,4-diaryl-2,5-dihydropyrroles with reduced hERG binding and employment of a phosphate prodrug strategy for aqueous solubility [J].