2. Academic Validation
  3. Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors

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

  • Eur J Med Chem. 2015 Sep 18:102:600-10. doi: 10.1016/j.ejmech.2015.08.031.
Daseul Im 1,  Kyungjin Jung 1,  Songyi Yang 1,  Waqar Aman 1,  Jung-Mi Hah 2
Affiliations

Affiliations

  • 1 Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do, 426-791, Republic of Korea.
  • 2 Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do, 426-791, Republic of Korea. Electronic address: jhah@hanyang.ac.kr.
PMID: 26318067 DOI: 10.1016/j.ejmech.2015.08.031
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.

Keywords

4-arylamido 3-methyl isoxazoles; Antiproliferative activity; Hematopoietic cell line; Kinase inhibitor; Kinase selectivity.

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