Loew G H, Sahakian R
J Med Chem. 1977 Jan;20(1):103-6. doi: 10.1021/jm00211a021.
A conformational study utilizing quantum chemical methods was performed on a family of antimalarial alpha-(piperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrenemethanols whose structures differ by the placement of the substituent on either the 2,3, or 4 position of the piperidyl ring. The antimalarial activity of these 3-substituted compounds has been shown experimentally to be highly stereospecific while the 2-substituted compounds are not and the 4-substituted compounds are inactive. In this study, such observed differences in behavior are correlated with conformational results and a pharmacophore is postulated. The identity of the active racemate of the 3-piperidyl compound is predicted.
利用量子化学方法对一类抗疟α-(哌啶基)-3,6-双(三氟甲基)-9-菲甲醇进行了构象研究，该类化合物的结构因哌啶环2、3或4位上取代基的位置不同而有所差异。实验表明，这些3-取代化合物的抗疟活性具有高度立体特异性，而2-取代化合物则不具有，4-取代化合物无活性。在本研究中，观察到的这种行为差异与构象结果相关，并提出了一个药效团。预测了3-哌啶基化合物活性外消旋体的结构。
