Discovery of 6-(difluoro(6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b] [1,2,4]triazin-3-yl)methyl)quinoline as a highly potent and selective c-Met inhibitor
文献类型：期刊论文
| 作者 | Zhan, Zhengsheng2; Peng, Xia1; Liu, Qiufeng3; Chen, Fang2; Ji, Yinchun1; Yao, Shanyan2; Xi, Yong1; Lin, Yipeng2; Chen, Tiantian3; Xu, Yechun3
|
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2016-06-30 |
| 卷号 | 116页码:239-251 |
| 关键词 | Antitumor c-Met Kinase inhibitor Triazolotriazines |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.03.076 |
| 文献子类 | Article |
| 英文摘要 | c-Met/HGF overexpression has been detected in many human malignancies including tumors which are resistant to anticancer therapy. Disrupting the aberrant c-Met/HGF axis has enjoyed significant progress in both preclinical and clinical antitumor campaign. To eliminate the OCH2-related metabolic deficiency of our previously reported triazolotriazine 2, we synthesized a series of CH2-/CF2-linked triazolotriazines and assessed their c-Met activities, leading to the highly potent compound 23 with IC50 values of 0.24 nM of enzymatic activity in c-Met and 0.85 nM of cellular activity in EBC-1 cancer cell line, as well as with complete tumor regression in EBC-1 xenograft mice model at dose of 25 mg/kg via oral administration. Based on its potent anti-proliferative activities and favorable pharmacokinetic properties, 23 has been selected as a drug candidate for preclinical investigation. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | FACTOR SCATTER FACTOR ; TYROSINE KINASE INHIBITOR ; GROWTH-FACTOR RECEPTOR ; SIGNALING PATHWAY ; INVASIVE GROWTH ; TARGETING MET ; CANCER ; METASTASIS ; PHENOTYPE ; CELLS |
| 资助项目 | National Natural Science Foundation of China[81273365] ; National Natural Science Foundation of China[81573271] ; National Natural Science Foundation of China[81422047] ; National Natural Science Foundation of China[81321092] ; National Natural Science Foundation of China[81473243] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09304002-008-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2012ZX09301001-007] ; Shanghai Science and Technology Commission[1315431901300] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000376803200024 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275983]  |
| 专题 | 药物发现与设计中心 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 药物化学研究室 药理学第一研究室 |
| 通讯作者 | Xu, Yechun; Ai, Jing; Geng, Meiyu; Duan, Wenhu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhan, Zhengsheng,Peng, Xia,Liu, Qiufeng,et al. Discovery of 6-(difluoro(6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b] [1,2,4]triazin-3-yl)methyl)quinoline as a highly potent and selective c-Met inhibitor[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2016,116:239-251. |
| APA | Zhan, Zhengsheng.,Peng, Xia.,Liu, Qiufeng.,Chen, Fang.,Ji, Yinchun.,...&Duan, Wenhu.(2016).Discovery of 6-(difluoro(6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b] [1,2,4]triazin-3-yl)methyl)quinoline as a highly potent and selective c-Met inhibitor.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,116,239-251. |
| MLA | Zhan, Zhengsheng,et al."Discovery of 6-(difluoro(6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b] [1,2,4]triazin-3-yl)methyl)quinoline as a highly potent and selective c-Met inhibitor".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 116(2016):239-251. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
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。