期刊
MEDICINAL CHEMISTRY RESEARCH
卷 22, 期 12, 页码 5961-5972出版社
SPRINGER BIRKHAUSER
DOI: 10.1007/s00044-013-0583-7
关键词
Pharmacophore; 3D-QSAR; Hydrophobic; GABA(A) receptor antagonist
资金
- National Natural Science Foundation of China [21172070]
- National Key Technology R&D Program of China [2011BAE06B05]
- National High Technology Research Development Program of China [2011AA 10A207]
- National Basic Research Program of China [2010CB126100]
- Fundamental Research Funds for the Central Universities
Pharmacophore modeling, comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) studies have been carried out on 5-(4-piperidyl)-3-isoxazolol (4-PIOL) analogs as GABA(A) receptor antagonists in this study. The best pharmacophore hypothesis generated by PHASE was ADHPR.6, which comprised a hydrogen bond acceptor (A), a hydrogen bond donor (D), a hydrophobic group (H), a positively charged group (P), and an aromatic ring (R). The pharmacophore model provided a good alignment for the further 3D-QSAR analyses, which presented a good R (2) value of 0.943, 0.930, and 0.916 for atom-based QSAR model, CoMFA model, and CoMSIA model, respectively. All QSAR models presented good statistical significance and predictivity, the corresponding Q (2) values for each 3D-QSAR model are 0.794, 0.569, and 0.637, respectively. Both pharmacophore and CoMSIA results showed that the hydrophobic sites are the key structural feature for GABA(A) receptor antagonists with high activities.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据