Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis
文献类型：期刊论文
| 作者 | Shi, Ying2; Duan, Yan-Hui3; Ji, Yue-Yang2; Wang, Zhi-Long4; Wu, Yan-Ran2; Gunosewoyo, Hendra5; Xie, Xiao-Yu6; Chen, Jian-Zhong6; Yang, Fan2; Li, Jing4
|
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-08-24 |
| 卷号 | 60期号:16页码:7067-7083 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.7b00724 |
| 文献子类 | Article |
| 英文摘要 | Selective CB2 agonists represent an attractive therapeutic strategy for the treatment of a variety of diseases without psychiatric side effects mediated by the CB1 receptor. We carried out a rational optimization of a black market designer drug SDB-001 that led to the identification of potent and selective CB2 agonists. A 7-methoxy or 7-methylthio substitution at the 3-amidoalkylindoles resulted in potent CB2 antagonists (27 or 28, IC50 = 1628 nM). Replacement of the amidoalkyls from 3-position to the 2-position of the indole ring dramatically increased the agonist selectivity on the CB2 over CB1 receptor. Particularly, compound 57 displayed a potent agonist activity on the CB2 receptor (EC50 = 114-142 nM) without observable agonist or antagonist activity on the CB1 receptor. Furthermore, 57 significantly alleviated the clinical symptoms and protected the murine central nervous system from immune damage in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. |
| WOS关键词 | PHARMACOLOGICAL CHARACTERIZATION ; CB2 RECEPTOR ; NEURODEGENERATIVE DISORDERS ; ENDOCANNABINOID SYSTEM ; BIOLOGICAL EVALUATION ; INTERNATIONAL UNION ; CRYSTAL-STRUCTURE ; LIGANDS ; ANTAGONISTS ; INDOLES |
| 资助项目 | Innovation Program of Shanghai Municipal Education Commission[15ZZ027] ; Ministry of Science and Technology[2014CB541906] ; National Natural Science Foundation of China[81425024] ; Open Program of State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM1501KF-05] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000408598500016 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272522]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Xie, Xin; Yu, Li-Fang |
| 作者单位 | 1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 2.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, 3663 Normal Zhongshan Rd, Shanghai 200062, Peoples R China; 3.Tongji Univ, Collaborat Innovat Ctr Brain Sci, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res,Lab Receptor, 1239 Siping Rd, Shanghai 200092, Peoples R China; 4.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China; 5.Curtin Univ, Fac Hlth Sci, Sch Pharm, Perth, WA 6102, Australia; 6.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Shi, Ying,Duan, Yan-Hui,Ji, Yue-Yang,et al. Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60(16):7067-7083. |
| APA | Shi, Ying.,Duan, Yan-Hui.,Ji, Yue-Yang.,Wang, Zhi-Long.,Wu, Yan-Ran.,...&Yu, Li-Fang.(2017).Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis.JOURNAL OF MEDICINAL CHEMISTRY,60(16),7067-7083. |
| MLA | Shi, Ying,et al."Amidoalkylindoles as Potent and Selective Cannabinoid Type 2 Receptor Agonists with in Vivo Efficacy in a Mouse Model of Multiple Sclerosis".JOURNAL OF MEDICINAL CHEMISTRY 60.16(2017):7067-7083. |
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。