Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors
文献类型：期刊论文
| 作者 | Dong Qian2; Peng Xia1; Wang Wen2; Dai Yang1; Zhao Weili2; Ai Jing1 ; Dong Xiaochun2
|
| 刊名 | CHINESE JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2015-09 |
| 卷号 | 35期号:9页码:1939-1947 |
| 关键词 | 5-aminopyrazole 5-amino-1,2,3-triazole FGFR inhibitors anti-tumor agent |
| ISSN号 | 0253-2786 |
| DOI | 10.6023/cjoc201503045 |
| 文献子类 | Article |
| 英文摘要 | Fibroblast growth factor receptor (FGFR) is a promising therapeutic target for cancer treatment. A series of 5-aminopyrazole and 5-amino-1,2,3-triazole derivatives were designed as FGFR inhibitors based on the docking mode of Debio1347 within the FGFR kinase domain. The inhibitory effects on FGFR2 kinase and the antitumor activities against human gastric cancer SNU16 cell lines were evaluated. Furthermore, the preliminary structure-activity relationships (SAR) was discussed. The results demonstrated that several compounds present good potency against FGFR2 kinase. (2-methyl-1H-benzo [d]imidazol-6-yl)-1H-pyrazol-4-yl)-1-(1H-thieno[3,2-b]pyrrol-2-yOmethanone (8) and 1-(5-amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-1,2,3-triazol-4-yl)-1-(1H-indol-2-yl)methanone (18) were the most potent with 1050 values of 3.3 and 2.3 nmol.L-1, respectively, which are similar to that of Debio1347. Compounds 8 and 18 exhibited slightly weaker antitumor activity against SNU16 cell lines than Debio1347 with IC50 value of 77.3, 155.2 nmol.L-1, respectively. |
| WOS关键词 | SELECTIVE INHIBITOR ; ACTIVATING MUTATIONS ; TYROSINE KINASE ; CANCER ; POTENT ; CARCINOMA ; FAMILY ; FGFR2 |
| 资助项目 | Specialized Research Fund for the Doctoral Program of Higher Education of China[20130071110071] ; Shanghai Municipal Science & Technology Pillar Program for Bio-pharmaceuticals[13431900102] |
| WOS研究方向 | Chemistry |
| 语种 | 中文 |
| CSCD记录号 | CSCD:5546049 |
| WOS记录号 | WOS:000364618100013 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276404]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Dong Qian |
| 作者单位 | 1.Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Dong Qian,Peng Xia,Wang Wen,et al. Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2015,35(9):1939-1947. |
| APA | Dong Qian.,Peng Xia.,Wang Wen.,Dai Yang.,Zhao Weili.,...&Dong Xiaochun.(2015).Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors.CHINESE JOURNAL OF ORGANIC CHEMISTRY,35(9),1939-1947. |
| MLA | Dong Qian,et al."Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors".CHINESE JOURNAL OF ORGANIC CHEMISTRY 35.9(2015):1939-1947. |
入库方式： OAI收割
来源：上海药物研究所
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