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Updated: Apr 30, 2026

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Published on: June 23, 2023
Optimization of diaryl amine derivatives as kinesin spindle protein inhibitors
Tomoki Takeuchi1, Shinya Oishi1, Masato Kaneda1
1Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
Structure-activity relationship studies of diaryl amine-type KSP inhibitors were carried out. Diaryl amine derivatives with a pyridine ring or urea group were less active when compared with the parent carboline and carbazole derivatives. Optimization studies of a lactam-fused diphenylamine-type KSP inhibitor revealed that the aniline NH group and 3-CF3 phenyl group were indispensable for potent KSP inhibition. Modification with a seven-membered lactam-fused phenyl group and a 4-(trifluoromethyl)pyridin-2-yl group improved aqueous solubility while maintaining potent KSP inhibitory activity. From these studies, we identified novel diaryl amine-type KSP inhibitors with a favorable balance of potency and solubility.
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