Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1.

Autor: Gryshchenko AA; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine. Electronic address: a.a.grischenko@imbg.org.ua., Bdzhola VG; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine., Balanda AO; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine., Briukhovetska NV; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine., Kotey IM; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine., Golub AG; Otava Ltd, 65 400 Applewood Crescent, Unit 100, Vaughan, Ontario L4K 0C3, Canada., Ruban TP; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine., Lukash LL; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine., Yarmoluk SM; Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2015 May 01; Vol. 23 (9), pp. 2287-93. Date of Electronic Publication: 2015 Mar 03.
DOI: 10.1016/j.bmc.2014.12.044
Abstrakt: Fibroblast grow factor receptor 1 (FGFR1) is an important anti-cancer target that plays crucial role in oncogenesis and oncogenic angiogenesis. The structure-activity relationship (SAR) of N-phenylthieno[2,3-d]pyrimidin-4-amines was investigated. Binding of active compounds with FGFR1 kinase was analyzed by molecular modeling studies. Selected active thieno[2,3-d]pyrimidines were tested for selectivity and antiproliferative activity. The most active compounds, 3-({6-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol and 3-({5-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol have IC₅₀ 0.16 and 0.18 μM, respectively. The results presented here may help to identify new thienopyrimidines with optimized cell growth inhibitory activity which may be further used as anticancer agents.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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