3D-QSAR CoMFA and CoMSIA on protein tyrosine phosphatase 1B inhibitors
3D-QSAR CoMFA and CoMSIA on protein tyrosine phosphatase 1B inhibitors
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DOI：
10.1016/s0968-0896(02)00056-1
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发表时间：
2002-07-01
影响因子：
3.5
通讯作者：
Kulkarni, VM
中科院分区：
文献类型：
--
作者：
Murthy, VS;Kulkarni, VM
对一系列苯并呋喃苯并噻吩联苯作为具有抗高血糖活性的蛋白酪氨酸磷酸酶1B （PTP 1B）抑制剂进行了3D-QSAR和分子建模。通过对92种化合物的评价建立了该模型，并通过对26种化合物的外部评价验证了该模型的有效性。利用模拟退火得到的活性化合物（化合物54）的最低能构象作为模板结构进行定向。CoMFA模型的RMS拟合和A log P作为附加描述符(r(cv)（2) = 0.615, r(2) = 0.842）和CoMSIA组合的空间、静电和亲脂场(r(cv)（2) = 0.597, r(2) = 0.910）获得了最好的预测结果。然后将3D-QSAR模型叠加到PTP 1B活性位点上，给出不同区域的直接等高线图。进一步比较3D-QSAR的等高线图，发现与PTP 1B酶的活性位点具有高度的相容性。(C) 2002 Elsevier Science Ltd.版权所有。
3D-QSAR and molecular modeling was performed on a series of benzofuran benzothiophene biphenyls as protein tyrosine phosphatase 1B (PTP 1B) inhibitors with anti-hyperglycemic activity. Evaluation of 92 compounds served to establish the model, which was validated by evaluation of an external set of 26 compounds. The lowest energy conformer of most active compound (compound 54) obtained from simulated annealing was used as a template structure for the alignment. The best predications were obtained with the CoMFA model from RMS fit and A log P as additional descriptor (r(cv)(2) = 0.615, r(2) = 0.842), and with the CoMSIA combined steric, electrostatic, and lipophilic fields (r(cv)(2) = 0.597, r(2) = 0.910). The 3D-QSAR model was then superimposed to the PTP 1B active site, giving direct contour maps of the different fields. Further comparison of the contour maps from the 3D-QSAR showed high level of compatibility with the active site of PTP 1B enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.