SUBSTITUTED 3-PHENYLTROPANE ANALOGS OF COCAINE - SYNTHESIS, INHIBITION OF BINDING AT COCAINE RECOGNITION SITES, AND POSITRON EMISSION TOMOGRAPHY IMAGING
SUBSTITUTED 3-PHENYLTROPANE ANALOGS OF COCAINE - SYNTHESIS, INHIBITION OF BINDING AT COCAINE RECOGNITION SITES, AND POSITRON EMISSION TOMOGRAPHY IMAGING
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DOI：
10.1021/jm00059a010
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发表时间：
1993-04-02
影响因子：
7.3
通讯作者：
MADRAS, BK
中科院分区：
文献类型：
--
作者：
MELTZER, PC;LIANG, AY;MADRAS, BK
现在公认的是，（-）-可卡因结合到与哺乳动物大脑中的单胺转运蛋白相关的特异性识别位点。在本研究中，制备了3 β-苯基托烷-2 β-羧酸甲酯的几种类似物，并评价了它们抑制[H-3]-3 β-（4-氟苯基）托烷-2 β-羧酸甲酯与灵长类动物尾壳核结合的效力。介绍了迄今报道的最有效的可卡因同系物之一3 β-（3，4-二氯苯基）托烷-2 β-羧酸甲酯的合成和结合亲和力。证明了合成可卡因识别位点的高亲和力配体的可行性及其作为体内可卡因受体的PET成像配体的适用性。
It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3beta-phenyltropane-2beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [H-3]-3beta-(4-fluorophenyl)tropane-2beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.