Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors
文献类型：期刊论文
| 作者 | Liu, Yang1; Guo, Lin2,3; Duan, Hongliang1; Zhang, Liming1; Jiang, Neng4; Zhen, Xuechu2,3; Shen, Jianhua1
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| 刊名 | RSC ADVANCES
 |
| 出版日期 | 2015 |
| 卷号 | 5期号:51页码:40964-40977 |
| ISSN号 | 2046-2069 |
| DOI | 10.1039/c5ra04714e |
| 文献子类 | Article |
| 英文摘要 | Regulation of glycine transporter 1 (GlyT1) activity is a currently investigated strategy in drug discovery for schizophrenia. This study developed a series of new 4-benzoylpiperidine derivatives as GlyT1 inhibitors by bioisosteric replacement and mimicking of the pyridine ring of RG1678. Among the 4-benzoylpiperidine derivatives, 23q showed an IC50 of 30 nM. Preliminary optimization of the blood-brain barrier penetration led to the discovery of 3-(piperidin-4-yl)benzo[d]isoxazole derivatives. Both series showed good selectivity over GlyT2, D-1, D-2, D-3, 5-HT1A and 5-HT2A receptors. Moreover, behavioral testing showed 23q (40 mg kg(-1), intragastric) can inhibit the hyperlocomotion induced by acute treatment of phencyclidine, and improve the impaired negative and cognitive symptoms in chronic phencyclidine-induced C57BL/6J mice. An interesting finding showed that 3-(piperidin-4-yl)benzo[d]isoxazole was a privileged scaffold of atypical antipsychotic agents but exhibited high selectivity and potency as a GlyT1 inhibitor. |
| WOS关键词 | GLYCINE TRANSPORTERS ; SCHIZOPHRENIA ; IDENTIFICATION ; DEFICITS |
| 资助项目 | National Nature Science Foundation of China[81402786] ; National Nature Science Foundation of China[81130023] ; National Basic Research Plan (973) of the Ministry of Science and Technology of China[2011CB5C4403] ; Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD)[00000000] ; Jiangsu Science and Technology Commission[BY2011131] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000354212300059 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276733]  |
| 专题 | 药理学第二研究室 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 药物发现与设计中心 药物化学研究室 |
| 通讯作者 | Shen, Jianhua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215006, Peoples R China; 3.Soochow Univ, Dept Pharmacol, Suzhou 215006, Peoples R China; 4.China Pharmaceut Univ, Nanjing 210009, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yang,Guo, Lin,Duan, Hongliang,et al. Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors[J]. RSC ADVANCES,2015,5(51):40964-40977. |
| APA | Liu, Yang.,Guo, Lin.,Duan, Hongliang.,Zhang, Liming.,Jiang, Neng.,...&Shen, Jianhua.(2015).Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors.RSC ADVANCES,5(51),40964-40977. |
| MLA | Liu, Yang,et al."Discovery of 4-benzoylpiperidine and 3-(piperidin-4-yl)benzo[d]isoxazole derivatives as potential and selective GlyT1 inhibitors".RSC ADVANCES 5.51(2015):40964-40977. |
入库方式： OAI收割
来源：上海药物研究所
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