Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate
文献类型：期刊论文
| 作者 | Zhang, Yang-Ming1,2 ; Xu, Hai-Yan1,3; Hu, Hai-Ning1; Tian, Fu-Yun1; Chen, Fei1; Liu, Hua-Nan1; Zhan, Li1; Pi, Xiao-Ping1; Liu, Jie4; Gao, Zhao-Bing1,3
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2021-05-13 |
| 卷号 | 64期号:9页码:5816-5837 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.0c02252 |
| 文献子类 | Article |
| 英文摘要 | We previously reported that P-retigabine (P-RTG), a retigabine (RTG) analogue bearing a propargyl group at the nitrogen atom in the linker of RTG, displayed moderate anticonvulsant efficacy. Recently, our further efforts led to the discovery of HN37 (pynegabine), which demonstrated satisfactory chemical stability upon deleting the ortho liable -NH2 group and installing two adjacent methyl groups to the carbamate motif. HN37 exhibited enhanced activation potency toward neuronal Kv7 channels and high in vivo efficacy in a range of pre-clinical seizure models, including the maximal electroshock test and a 6 Hz model of pharmacoresistant limbic seizures. With its improved chemical stability, strong efficacy, and better safety margin, HN37 has progressed to clinical trial in China for epilepsy treatment. |
| WOS关键词 | ANIMAL-MODELS ; PHARMACOLOGICAL CHARACTERIZATION ; CHANNEL AGONISTS ; EPILEPSY ; RETIGABINE ; EZOGABINE ; DISCOLORATION ; OPENER ; MODULATION ; UNDERLIE |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000651785800035 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309390]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Gao, Zhao-Bing; Nan, Fa-Jun |
| 作者单位 | 1.Chinese Acad Sci, Chinese Natl Ctr Drug Screening, Shanghai Inst Mat Med, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China; 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China; 4.Hainan Haiyao Co Ltd, Haikou 570311, Hainan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Yang-Ming,Xu, Hai-Yan,Hu, Hai-Ning,et al. Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate[J]. JOURNAL OF MEDICINAL CHEMISTRY,2021,64(9):5816-5837. |
| APA | Zhang, Yang-Ming.,Xu, Hai-Yan.,Hu, Hai-Ning.,Tian, Fu-Yun.,Chen, Fei.,...&Nan, Fa-Jun.(2021).Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate.JOURNAL OF MEDICINAL CHEMISTRY,64(9),5816-5837. |
| MLA | Zhang, Yang-Ming,et al."Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate".JOURNAL OF MEDICINAL CHEMISTRY 64.9(2021):5816-5837. |
入库方式： OAI收割
来源：上海药物研究所
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