title: Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1.
abstract: 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.
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine. Electronic address: a.a.grischenko@imbg.org.ua.
authors: A A
authors: AA
authors: Gryshchenko
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: V G
authors: VG
authors: Bdzhola
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: A O
authors: AO
authors: Balanda
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: N V
authors: NV
authors: Briukhovetska
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: I M
authors: IM
authors: Kotey
authors: Otava Ltd, 65 400 Applewood Crescent, Unit 100, Vaughan, Ontario L4K 0C3, Canada.
authors: A G
authors: AG
authors: Golub
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: T P
authors: TP
authors: Ruban
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: L L
authors: LL
authors: Lukash
authors: Institute of Molecular Biology and Genetics NAS of Ukraine, 150 Akademika Zabolotnogo Str., Kyiv 03680, Ukraine.
authors: S M
authors: SM
authors: Yarmoluk
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013876:Thiophenes; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Drug design; FGFR1 inhibitor; Molecular modeling; Thienopyrimidines