文献类型：期刊文献

英文题名：Comparative pharmacophore modeling of human adenosine receptor A1 and A3 antagonists

作者：Xu ZheJun[1];Cheng FeiXiong[1];Li Jie[1];Zhou YaDi[1];Su Ni[1];Li WeiHua[1];Liu GuiXia[1];Tang Yun[1]

机构：[1]E China Univ Sci & Technol, Dept Pharmaceut Sci, Sch Pharm, Shanghai 200237, Peoples R China

年份：2012

卷号：55

期号：11

起止页码：2407

外文期刊名：SCIENCE CHINA-CHEMISTRY

收录：;EI(收录号：20130315905262);WOS:【SCI-EXPANDED(收录号:WOS:000311301300019)】；

基金：This work was supported by the National Natural Science Foundation of China (21072059), the Program for New Century Excellent Talents in University (NCET-08-0774), the 111 Project (B07023), the Shanghai Committee of Science and Technology (11DZ2260600), the Fundamental Research Funds for the Central Universities (WY1113007) and the National S&T Major Project of China (2009ZX09501-001).

语种：英文

外文关键词：pharmacophore modeling; adenosine receptors; antagonists; enrichment factor; simulated virtual screening

摘要：Adenosine receptors are promising therapeutic targets in drug discovery. In this study, three-dimensional pharmacophore models of human adenosine receptor A(1) and A(3) antagonists were developed based on 26 and 23 diverse compounds, respectively. The best A(1) pharmacophore model (A(1)_Hopy1) consists of four features: one hydrogen bond donor, one hydrophobic point and two ring aromatics, while the best A(3) pharmacophore model (A(3)_Hopy1) also has four features: one hydrogen bond acceptor, one hydrophobic point and two ring aromatics. The correlation coefficients were 0.840 for A(1) test set with 146 diverse compounds and 0.827 for A(3) test set with 238 diverse compounds. In the simulated virtual screening experiments, high enrichment factors of 6.51 and 6.90 were obtained for A(1)_Hopy1 and A(3)_Hopy1 models, respectively. Moreover, two models also showed high subtype-selectivity in the simulated virtual screening experiments. These results could be helpful for the discovery of novel potent and selective A(1) and A(3) antagonists.