Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines
文献类型：期刊论文
| 作者 | Liu, Zhili2; Chen, Xuetao1; Yu, Leiping1; Zhen, Xuechu1; Zhang, Ao2
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2008-07-15 |
| 卷号 | 16期号:14页码:6675-6681 |
| 关键词 | aminothiazole apomorphine dopamine receptor hybridize serotonin receptor |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2008.05.077 |
| 文献子类 | Article; Proceedings Paper |
| 英文摘要 | A series of apomorphine ((-)-1, APO)-derived analogues ((+/-)-3,(-)-4-(-)-6) were designed and synthesized by hybridizing APO with a privileged 2-aminothiazole functionality which was lent from the orally available anti-parkinsonian drug, pramipexole (2). Among these hybridized compounds, catecholic aporphine (-)-6 shows good affinity at the D(2) receptor with K(i) of 328 nM, slightly less potent (3-fold), but more selective against the D(1) receptor than that of the parent compound, APO. Although possessing reduced affinity at the D(2) receptor, aporphines 15 and 18 show significant potency at both the D(1) and 5-HT(1A) receptors. The former compound is equipotent at both receptors (K(i): 116 and 151 nM, respectively), while the latter is 8-fold more potent at the D(1) (K(i): 78 nM) than at the 5-HT(1A) receptors (K(i): 640 nM). These results indicate that the catechol fragment is critical for the D(2) receptor binding of the anti-parkinsonian drug, APO ((-)-1), but not necessary for binding at the D(1) and 5-HT(1A) receptors. (c) 2008 Elsevier Ltd. All rights reserved. |
| WOS关键词 | DOPAMINE-RECEPTOR AFFINITIES ; (R)-APORPHINES SYNTHESIS ; O-DEMETHYLATION ; APOMORPHINE ; DERIVATIVES ; AGONISTS ; DISEASE |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000257829600003 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272865]  |
| 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.Chinese Acad Sci, SIMM, Neuropharmacol Lab, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, SIMM, SOMCL, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Zhili,Chen, Xuetao,Yu, Leiping,et al. Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2008,16(14):6675-6681. |
| APA | Liu, Zhili,Chen, Xuetao,Yu, Leiping,Zhen, Xuechu,&Zhang, Ao.(2008).Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines.BIOORGANIC & MEDICINAL CHEMISTRY,16(14),6675-6681. |
| MLA | Liu, Zhili,et al."Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines".BIOORGANIC & MEDICINAL CHEMISTRY 16.14(2008):6675-6681. |
入库方式： OAI收割
来源：上海药物研究所
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