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

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.

Graphical abstract1,4-Diaryl-4,5-dihydropyrazoles (i.e., 25) are reported as potent inhibitors of the mitotic kinesin KSP.Figure optionsDownload full-size imageDownload as PowerPoint slide