Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR
文献类型：期刊论文
| 作者 | Zhang, Qiumeng1,3; Shen, Qianqian2; Gao, Lixin3; Tong, Linjiang2; Li, Jia3 ; Chen, Yi2; Lu, Wei1
|
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2018-10-05 |
| 卷号 | 158页码:428-441 |
| 关键词 | Aurora A Aurora B KDR Multi-targeted Anticancer Heterocyclic |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2018.09.032 |
| 文献子类 | Article |
| 英文摘要 | Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play essential roles in sustained cancer growth. In the present study, eighteen pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora A/B and KDR) activities. Among these analogs, compound 17g displayed significant Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM, respectively. The results of further biological assays showed that compound 17g possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74 cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC-7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F = 63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine could be developed as a promising scaffold of multiple Aurora A/B and KDR inhibitors and 17g was worth of further research as a multi-targeted lead compound. (C) 2018 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | VEGFR-2 INHIBITORS ; KINASE INHIBITORS ; GROWTH-FACTOR ; SOLID TUMORS ; ORAL AURORA ; CANCER ; ANGIOGENESIS ; DISCOVERY ; SORAFENIB ; SUNITINIB |
| 资助项目 | National Natural Science Foundation of China[81402953] ; Shanghai Science and Technology Council[16DZ2280100] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000448094000031 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279538]  |
| 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 国家新药筛选中心 |
| 通讯作者 | Chen, Yi; Lu, Wei |
| 作者单位 | 1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Qiumeng,Shen, Qianqian,Gao, Lixin,et al. Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,158:428-441. |
| APA | Zhang, Qiumeng.,Shen, Qianqian.,Gao, Lixin.,Tong, Linjiang.,Li, Jia.,...&Lu, Wei.(2018).Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,158,428-441. |
| MLA | Zhang, Qiumeng,et al."Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted inhibitors of Aurora A/B and KDR".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 158(2018):428-441. |
入库方式： OAI收割
来源：上海药物研究所
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