Jin B, Hopfinger A J
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60680.
J Chem Inf Comput Sci. 1994 Jul-Aug;34(4):1014-21. doi: 10.1021/ci00020a041.
Four pharmacophore recognition sites have been proposed for active thromboxane A2 (TxA2) antagonists. We have sought to define the corresponding spatial pharmacophore for these four sites by performing conformational analysis and molecular superposition studies on five known antagonists: SQ 29,548, SQ 28,668, SQ 27,427, BM 13.505, and a Merck Frosst compound. The strategy was to identify a low intramolecular-energy conformer state for each antagonist for which the relative locations and orientations of the corresponding recognition site groups were in common when all five antagonists were superimposed. The conformations used in the successful molecular superpositions were then postulated to be the active conformations of each antagonist. Since SQ 29,548 is the most potent of the five antagonists, it was considered the reference structure in the molecular superposition. A unique spatial pharmacophore was identified and may be a useful template in designing a new TxA2 antagonists.
对于活性血栓素A2（TxA2）拮抗剂，已提出四个药效团识别位点。我们试图通过对五种已知拮抗剂进行构象分析和分子叠加研究来确定这四个位点相应的空间药效团，这五种拮抗剂分别是：SQ 29,548、SQ 28,668、SQ 27,427、BM 13.505以及默克弗罗斯特公司的一种化合物。策略是为每种拮抗剂确定一种低分子内能量构象状态，当所有五种拮抗剂叠加时，相应识别位点基团的相对位置和取向具有共性。然后将成功进行分子叠加时所使用的构象假定为每种拮抗剂的活性构象。由于SQ 29,548是这五种拮抗剂中活性最强的，因此在分子叠加中被视为参考结构。确定了一种独特的空间药效团，它可能是设计新型TxA2拮抗剂的有用模板。
