Pharmacophore models and 3D-QSAR studies of rat and fly's GABA receptor inhibitors

采用 DISCOtech方法 ,用 7个大鼠 γ-氨基丁酸 (GABA) A 受体抑制剂和 1 1个家蝇 GABAA 受体抑制剂分别建立了其药效团模型 ;用 Co MFA方法建立了 2 2个大鼠 GABAA 受体抑制剂和 2 9个家蝇 GABAA 受体抑制剂的 3 D-QSAR模型 ,模型的交叉验证相关系数分别为 0 .5 2 6和 0 .679,验证了药效团模型的合理性 ,为设计更高活性和更高选择性的化合物提供了参考gamma-Aminobutyric acid(GABA) plays an important role as a major inhibitory neurotransmitter in both vertebrates and invertebrates, which have similar but pharmacologically distinct GABA(A) receptors, so insects' GABA(A) receptors are regarded as a promising target for insecticides. In this paper, two pharmacophore models of rat and fly's GABA(A) receptors for a series of reported inhibitors were studied by DIS-COtech methodology, which laid a foundation for finding the leading compounds and designing new selective compounds. According to this study, the three-dimensional quantitative structure and activity relationships were studied, which gave two predictive CoMFA models with q(rat)(2), = 0.526 and q(fly)(2) = 0.679. The CoMFA models verified the pharmacophore models, and gave insights to the design of better GABA(A) receptor inhibitors.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000228021800035&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701SCI(E)中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)503546-5492