Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors

European Journal of Medicinal Chemistry
Daseul ImJung-Mi Hah

Abstract

A series of 4-arylamido 3-methyl isoxazoles were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Most compounds showed selective antiproliferative activity toward the U937 cell line and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide 5a-b, 6a-o and urea 7a-n, 8a-g with hydrophobic moieties, and one of the most potent inhibitor 6a, 5-methyl-N-(2-methyl-5-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamido)phenyl)isoxazole-4-carboxamide was found to be very potent inhibitor of FMS kinase (GI50 = 0.016 μM, IC50 = 9.95 nM) with excellent selectivity profiles and is a promising candidate for further development in therapeutics for cancer.

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Citations

Aug 4, 2016·European Journal of Medicinal Chemistry·Verónica AlcoleaCarmen Sanmartín
Aug 3, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nuria Díaz-ArgelichCarmen Sanmartín
Dec 7, 2018·Current Medicinal Chemistry·Maria A ChiacchioLaura Legnani
Apr 28, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Daseul ImJung-Mi Hah
Jun 20, 2019·Current Medicinal Chemistry·Qiuju XunXiaoyun Lu
Jan 1, 2018·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Neetu Agrawal, Pradeep Mishra
Jan 20, 2021·Clinical and Translational Medicine·Neng WangZhiyu Wang
May 18, 2021·European Journal of Medicinal Chemistry·Girish Chandra AryaVikas Jaitak
Jan 3, 2018·Journal of Medicinal Chemistry·Mohammed I El-GamalChang-Hyun Oh
Apr 22, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Archana KumariRajesh K Singh

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