Design and optimization of purine derivatives as in vivo active PDE10A inhibitors
文献类型：期刊论文
| 作者 | Chen, Liu1,2; Chen, Danqi2 ; Tang, Le1,2; Ren, Jing2; Chen, Jiaojiao3; Zhen, Xuechu3; Liu, Yu-Chih4; Zhang, Chenhua4; Luo, Haibin5; Shen, Jingkang2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-07-01 |
| 卷号 | 25期号:13页码:3315-3329 |
| ISSN号 | 0968-0896 |
| 关键词 | Phosphodiesterase PDE10A Purine Inhibitor Anti-psychotic |
| DOI | 10.1016/j.bmc.2017.04.019 |
| 文献子类 | Article |
| 英文摘要 | Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2-alpyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity. And after further PDE enzymatic selectivity study, metabolic stability assay and in vivo pharmacological tests we identified two inhibitors as interesting lead compounds with the potential for further PDE10A lead optimizatioin. (C) 2017 Elsevier Ltd. All rights reserved. |
| WOS关键词 | CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES ; ANIMAL-MODELS ; SCHIZOPHRENIA ; DISCOVERY ; DISEASES ; POTENT ; IDENTIFICATION ; TARGETS |
| 资助项目 | National Natural Science Foundation of China[81273368] ; National Natural Science Foundation of China[81330076] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2014ZX09507-002] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:000402941700005 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272594]  |
| 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 | Shen, Jingkang; Xiong, Bing |
| 作者单位 | 1.Nanchang Univ, Sch Pharmaceut Sci, Nanchang 330006, Jiangxi, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Soochow Univ, Dept Pharmacol, Coll Pharmaceut Sci, Suzhou, Peoples R China; 4.Shanghai ChemPartner Co LTD, Pudong New Area, Bldg 5,998 Halei Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China; 5.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Liu,Chen, Danqi,Tang, Le,et al. Design and optimization of purine derivatives as in vivo active PDE10A inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2017,25(13):3315-3329. |
| APA | Chen, Liu.,Chen, Danqi.,Tang, Le.,Ren, Jing.,Chen, Jiaojiao.,...&Xiong, Bing.(2017).Design and optimization of purine derivatives as in vivo active PDE10A inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY,25(13),3315-3329. |
| MLA | Chen, Liu,et al."Design and optimization of purine derivatives as in vivo active PDE10A inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY 25.13(2017):3315-3329. |
入库方式： OAI收割
来源：上海药物研究所
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