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
- 作者：Paul J. Coleman ; John D. Schreier ; Christopher D. Cox ; Mark E. Fraley ; Robert M. Garbaccio ; Carolyn A. Buser ; Eileen S. Walsh ; Kelly Hamilton ; Robert B. Lobell ; Keith Rickert ; Weikang Tao ; Ronald E. D
- 关键词：Cancer ; Kinesin spindle protein ; KSP inhibitors ; Antimitotics ; Dihydropyrazoles ; P-Glycoprotein
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 October 2007
- 卷：17
- 期：19
- 页码：5390-5395
- 文件大小：167 K
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.