Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors
文献类型：期刊论文
| 作者 | Hu, Suwen1; Gu, Quan1; Wang, Zhilong2; Weng, Zhiyong1; Cai, Yunrui1; Dong, Xiaowu1; Hu, Yongzhou1; Liu, Tao1; Xie, Xin2
|
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2014-01 |
| 卷号 | 71页码:259-266 |
| 关键词 | CCR5 inhibitor Anti-HIV-1 agent Piperidine-4-carboxamide derivatives |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2013.11.013 |
| 文献子类 | Article |
| 英文摘要 | Based on a putative 'Y shape' pharmacophore model of CCR5 inhibitors, a series of novel piperidine-4-carboxamide derivatives were designed and synthesized using a group-reverse strategy. Among synthesized target compounds, 16g (IC50 = 25.73 nM) and 16i (IC50 = 25.53 nM) showed equivalent inhibitory activity against CCR5 to that of the positive control maraviroc (IC50 = 25.43 nM) in calcium mobilization assay. Selected compounds were further tested for their antiviral activity in HIV-1 single cycle assay. Two compounds, 16g and 16i, displayed antiviral activity with IC50 values of 73.01 nM and 94.10 nM, respectively. Additionally, the pharmacokinetic properties and inhibitory potency against hERG of 16g were evaluated, providing a foundation for ongoing optimization. (C) 2013 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | SMALL-MOLECULE CCR5 ; ANTAGONIST TAK-220 ; HIV ; INFECTION ; RECEPTOR ; ENTRY |
| 资助项目 | National Natural Science Foundation of China[81072515] ; National Natural Science Foundation of China[81202341] ; Ministry of Science and Technology of China[2012ZX09301001-005] ; Ministry of Health-medical Science Critical Technological Program of Zhejiang Province[WKJ20122024] ; Shanghai Commission of Science and Technology[12XD1402100] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000331496100025 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277305]  |
| 专题 | 国家新药筛选中心 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 |
| 通讯作者 | Liu, Tao |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Suwen,Gu, Quan,Wang, Zhilong,et al. Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2014,71:259-266. |
| APA | Hu, Suwen.,Gu, Quan.,Wang, Zhilong.,Weng, Zhiyong.,Cai, Yunrui.,...&Xie, Xin.(2014).Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,71,259-266. |
| MLA | Hu, Suwen,et al."Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 71(2014):259-266. |
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。