Design, synthesis and evaluation of benzo[a]thieno[3,2-g]quinolizines as novel l-SPD derivatives possessing dopamine D-1, D-2 and serotonin 5-HT1A multiple action profiles
文献类型：期刊论文
| 作者 | Li, Zeng4; Huang, Jiye2; Sun, Haifeng4; Zhou, Shengbin4; Guo, Lin1,3,4; Zhou, Yu4 ; Zhen, Xuechu1,2,3; Liu, Hong4
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2014-11-01 |
| 卷号 | 22期号:21页码:5838-5846 |
| 关键词 | l-SPD Tetrahydroprotoberberine Dopamine receptor Serotonin receptor Multiple action |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2014.09.024 |
| 文献子类 | Article |
| 英文摘要 | A novel scaffold derived from l-SPD with a substituted thiophene group in the D ring were designed, synthesized, and evaluated for their binding affinities at dopamine (D-1, D-2 and D-3) and serotonin (5-HT1A and 5-HT2A) receptors. Most of the tetracyclic compounds exhibited higher affinities for D-2 and 5-HT1A receptors than l-SPD, while compound 23e showed the highest K-i value of 7.54 nM at D-2 receptor which was 14 times more potent than l-SPD. Additionally, compounds 23d and 23e were more potent than l-SPD at D-3 receptor. According to the functional assays, 23d and 23e were demonstrated as full antagonists at D-1 and D-2 receptors and full agonists at 5-HT1A receptor. Since the combination of D-2 antagonism and 5-HT1A agonism is considered effective in treating both the positive and negative symptoms of schizophrenia, these novel compounds are implicated as potential therapeutic agents. (C) 2014 Published by Elsevier Ltd. |
| WOS关键词 | D1 RECEPTOR AGONIST ; ANTIPSYCHOTIC-DRUG ; L-STEPHOLIDINE ; TETRAHYDROPROTOBERBERINE DERIVATIVES ; SCHIZOPHRENIA ; ANTAGONIST ; RAT ; TETRAHYDROPALMATINE ; PHARMACOLOGY ; ACTIVATION |
| 资助项目 | National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81025017] ; National Natural Science Foundation of China[81130023] ; National Natural Science Foundation of China[81373382] ; National Basic Research Plan (973) of the Ministry of Science and Technology of China[2011CB5C4403] ; National S&T Major Projects[2012ZX09103101-072] ; National S&T Major Projects[2012ZX09301001-005] ; National S&T Major Projects[2013ZX09507-001] ; Program of Shanghai Subject Chief Scientist[12XD1407100] ; Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD) from Jiangsu Science and Technology commission[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000344471800014 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276852]  |
| 专题 | 药理学第二研究室 药物化学研究室 |
| 通讯作者 | Zhen, Xuechu |
| 作者单位 | 1.Soochow Univ, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Coll Pharmaceut Sci, Suzhou, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China; 3.Soochow Univ, Dept Pharmacol, Coll Pharmaceut Sci, Suzhou, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Zeng,Huang, Jiye,Sun, Haifeng,et al. Design, synthesis and evaluation of benzo[a]thieno[3,2-g]quinolizines as novel l-SPD derivatives possessing dopamine D-1, D-2 and serotonin 5-HT1A multiple action profiles[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2014,22(21):5838-5846. |
| APA | Li, Zeng.,Huang, Jiye.,Sun, Haifeng.,Zhou, Shengbin.,Guo, Lin.,...&Liu, Hong.(2014).Design, synthesis and evaluation of benzo[a]thieno[3,2-g]quinolizines as novel l-SPD derivatives possessing dopamine D-1, D-2 and serotonin 5-HT1A multiple action profiles.BIOORGANIC & MEDICINAL CHEMISTRY,22(21),5838-5846. |
| MLA | Li, Zeng,et al."Design, synthesis and evaluation of benzo[a]thieno[3,2-g]quinolizines as novel l-SPD derivatives possessing dopamine D-1, D-2 and serotonin 5-HT1A multiple action profiles".BIOORGANIC & MEDICINAL CHEMISTRY 22.21(2014):5838-5846. |
入库方式： OAI收割
来源：上海药物研究所
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