Title of article :
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
Author/Authors :
Paul J. Coleman، نويسنده , , John D. Schreier، نويسنده , , Christopher D. Cox، نويسنده , , Mark E. Fraley، نويسنده , , Robert M. Garbaccio، نويسنده , , Carolyn A. Buser، نويسنده , , Eileen S. Walsh، نويسنده , , Kelly Hamilton، نويسنده , , Robert B. Lobell، نويسنده , , Keith Rickert، نويسنده , , Weikang Tao، نويسنده , , Ronald E. Diehl، نويسنده , , Vicki J. South، نويسنده , , Joseph P. Davide، نويسنده , , Nancy E. Kohl، نويسنده , , Youwei Yan، نويسنده , , Lawrence Kuo، نويسنده , , Thomayant Prueksaritanont، نويسنده , , Chunze Li، نويسنده , , Elizabeth A. Mahan، نويسنده , , et al.، نويسنده ,
Abstract :
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.
Keywords :
Kinesin spindle protein , KSP inhibitors , Dihydropyrazoles , Antimitotics , P-glycoprotein , CANCER
