Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties
文献类型：期刊论文
| 作者 | Zeng, Li-Fan2; Wang, Yong2; Kazemi, Roza3; Xu, Shili3; Xu, Zhong-Liang2; Sanchez, Tino W.3; Yang, Liu-Meng1,4; Debnath, Bikash3; Odde, Srinivas3; Xie, Hua2
|
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2012-11-22 |
| 卷号 | 55期号:22页码:9492-9509 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm300667v |
| 文献子类 | Article |
| 英文摘要 | Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories. In spite of its remarkable potency and efficacy, unfortunately upon completion of phase I clinical studies, development of L-870,810 was halted. Because of its desirable pharmacological and pharmaceutical properties we were intrigued to design novel analogues of L-870,810 with goals to (1) improve upon limitations of naphthyridine-7-carboxamides as antiviral agents and (2) to reposition their use as innovative cytotoxic agents for cancer therapeutics. Herein, we report on the design and synthesis of a series of 1,6-naphthyridine-7-carboxamides with various substitutions at the 5- and 8-positions. All the new 5-substituted-8-hydroxy-[1,6]naphthyridines were potent IN inhibitors and the 5-substituted-8-amino-[1,6]naphthyridines were significantly cytotoxic. Further optimization of the 5,8-disubstituted-[1,6]naphthyridines with structural variation on 7-carboxamide delivered novel compounds with significant cytotoxicity in a panel of cancer cell lines and effective inhibition against select oncogenic kinases. |
| WOS关键词 | CYTOMEGALOVIRUS HCMV INHIBITORS ; STRAND-TRANSFER ; MOLECULAR-MECHANISMS ; VIRAL REPLICATION ; POTENT ; DESIGN ; CELLS ; RECEPTOR-1 ; RESISTANCE ; DISCOVERY |
| 资助项目 | National Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[81072527] ; National Natural Science Foundation of China[81123004] ; National Natural Science Foundation of China[81102483] ; Key Scientific and Technological Program of China[2012ZX10001-006] ; Sharon and William Cockrell Endowed Cancer Research Fund[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000311461500008 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277873]  |
| 专题 | 药物化学研究室 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 | Long, Ya-Qiu |
| 作者单位 | 1.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan Province, Peoples R China; 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China; 3.Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA; 4.Chinese Acad Sci, Kunming Inst Zool, Kunming 650223, Yunnan Province, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zeng, Li-Fan,Wang, Yong,Kazemi, Roza,et al. Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties[J]. JOURNAL OF MEDICINAL CHEMISTRY,2012,55(22):9492-9509. |
| APA | Zeng, Li-Fan.,Wang, Yong.,Kazemi, Roza.,Xu, Shili.,Xu, Zhong-Liang.,...&Long, Ya-Qiu.(2012).Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties.JOURNAL OF MEDICINAL CHEMISTRY,55(22),9492-9509. |
| MLA | Zeng, Li-Fan,et al."Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties".JOURNAL OF MEDICINAL CHEMISTRY 55.22(2012):9492-9509. |
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。