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Design, synthesis and biological evaluation of naphthostyril derivatives as novel protein kinase FGFR1 inhibitors.

J Enzyme Inhib Med Chem.. 2014-06;

Gryshchenko AA, Levchenko KV, Bdzhola VG, Ruban TP, Lukash LL, Yarmoluk SM. Medicinal Chemistry Department, Institute of Molecular Biology and Genetics, Zabolotnogo str. 150, 03680 Kiev, Ukraine.

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摘要

New class of FGFR1 kinase inhibitors with naphthostyril heterocycle has been identified. A series of N-phenylnaphthostyril-1-sulfonamides has been synthesized and tested in vitro. It was revealed that the most active compound N-(4-hydroxyphenyl)naphthostyril-1-sulfonamide inhibited FGFR1 with IC50 of 2 μM. In our preliminary studies, N-phenylnaphthostyril-1-sulfonamides demonstrated selectivity of FGFR1 inhibition and antiproliferative activity on cancer cell line. N-phenylnaphthostyril-1-sulfonamides have a good potential for further development as anticancer agents.