Design and Synthesis of 5-Aminopyrazole and 5-Aminotriazole Derivatives as Fibroblast Growth Factor Receptor Inhibitors | |
Dong Qian2; Peng Xia1; Wang Wen2; Dai Yang1; Zhao Weili2; Ai Jing1![]() | |
刊名 | CHINESE JOURNAL OF ORGANIC CHEMISTRY
![]() |
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. |
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关键词 | SELECTIVE INHIBITOR ; ACTIVATING MUTATIONS ; TYROSINE KINASE ; CANCER ; POTENT ; CARCINOMA ; FAMILY ; FGFR2 |
WOS研究方向 | Chemistry |
语种 | 中文 |
CSCD记录号 | CSCD:5546049 |
出版者 | SCIENCE PRESS |
WOS记录号 | WOS:000364618100013 |
内容类型 | 期刊论文 |
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. |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论