Bourguignon J J, Schoenfelder A, Schmitt M, Wermuth C G, Hechler V, Charlier B, Maitre M
Département de Pharmacochimie Moléculaire, Centre de Neurochimie du CNRS, Strasbourg, France.
J Med Chem. 1988 May;31(5):893-7. doi: 10.1021/jm00400a001.
Substituted 4-hydroxybutyric (GHB) or trans-4-hydroxycrotonic acids (T-HCA) and structurally related compounds were synthesized and submitted to [3H]GHB binding. Structure-activity relationships studies highlighted for [3H]GHB binding (a) the necessity of a nonlactonic, relatively extended conformation of the gamma-hydroxybutyric chain, (b) the existence of some bulk tolerance in the vicinity of the hydroxyl group, and (c) the high sensitivity toward isosteric replacements of the carboxyl or the hydroxyl groups. T-HCA has been recently identified as a naturally occurring substance in the central nervous system (CNS) and shows a better affinity than GHB. Our findings are in favor of the presence in the CNS of specific GHB binding sites, which are different from the GABA and the picrotoxin binding sites, and for which T-HCA may be an endogenous ligand.
合成了取代的4-羟基丁酸（GHB）或反式-4-羟基巴豆酸（T-HCA）及其结构相关化合物，并进行了[3H]GHB结合实验。构效关系研究突出了[3H]GHB结合的以下几点：（a）γ-羟基丁酸链需要非内酯、相对伸展的构象；（b）羟基附近存在一定的体积耐受性；（c）对羧基或羟基的等排取代具有高敏感性。T-HCA最近被鉴定为中枢神经系统（CNS）中的一种天然物质，并且显示出比GHB更好的亲和力。我们的研究结果支持CNS中存在特定的GHB结合位点，这些位点不同于GABA和印防己毒素结合位点，并且T-HCA可能是其内源配体。
