Liljefors T, Bøgesø K P, Hyttel J, Wikström H, Svensson K, Carlsson A
Organic Chemistry 3, Chemical Center, University of Lund, Sweden.
J Med Chem. 1990 Mar;33(3):1015-22. doi: 10.1021/jm00165a020.
Pre- and postsynaptic dopaminergic activities of a series of indolizidine and quinolizidine analogues of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP) have been studied. The pharmacological data have been interpreted in terms of a previously reported model for interactions with dopamine pre- and postsynaptic D2-receptors and molecular mechanics (MM2(85] calculated geometries and conformational energies. The model has been further developed with respect to the receptor topography in the vicinity of the nitrogen binding site. In particular, a novel spatial orientation of the important "propyl cleft" has been proposed. This cleft is suggested to be located mainly above a plane through the receptor-bound substrate. The biologically active agonist and antagonist conformations of the enantiomers of 3-PPP have been reinvestigated.
对一系列3-(3-羟基苯基)-N-(正丙基)哌啶(3-PPP)的吲哚里西啶和喹诺里西啶类似物的突触前和突触后多巴胺能活性进行了研究。根据先前报道的与多巴胺突触前和突触后D2受体相互作用的模型以及分子力学(MM2[85]计算的几何结构和构象能量)对药理学数据进行了解释。该模型在氮结合位点附近的受体拓扑结构方面得到了进一步发展。特别是，提出了重要的“丙基裂隙”的一种新的空间取向。该裂隙被认为主要位于通过受体结合底物的平面上方。对3-PPP对映体的生物活性激动剂和拮抗剂构象进行了重新研究。
