کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1357667 | 981267 | 2016 | 7 صفحه PDF | دانلود رایگان |

Fibroblast growth factor receptor 1 (FGFR1) plays an important role in tumorigenesis and is therefore an attractive target for anticancer therapy. Using molecular docking approach we have identified inhibitor of FGFR1 belonging to 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones with IC50 value of 3.5 μM. A series of derivatives of this chemical scaffold has been synthesized and evaluated for inhibition of FGFR1 kinase activity. It was revealed that the most promising compounds 5-amino-1-(3-hydroxy-phenyl)-4-(6-methyl-1H-benzoimidazol-2-yl)-1,2-dihydro-pyrrol-3-one and 5-amino-4-(1H-benzoimidazol-2-yl)-1-(3-hydroxy-phenyl)-1,2-dihydro-pyrrol-3-one inhibit FGFR1 with IC50 values of 0.63 and 0.32 μM, respectively, and posses antiproliferative activity against KG1 myeloma cell line with IC50 values of 5.6 and 9.3 μM. Structure–activity relationships have been studied and binding mode of this chemical class has been proposed.
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Journal: Bioorganic & Medicinal Chemistry - Volume 24, Issue 9, 1 May 2016, Pages 2053–2059