A series of 2′‐substituted cocaine analogs (4‐8) was prepared and evaluated in an in vitro dopamine transporter (DAT) binding assay. Compounds 4‐7 were prepared by esterifying the 3β‐hydroxyl group of ecgonine methyl ester (3) using the appropriate acid chloride in the presence of Et3N and benzene. Compound 3 was obtained from cocaine (1) by hydrolysis using 1N HCl to afford ecgonine . HCl which was subjected to acid catalyzed esterification using methanol saturated with HCl gas. Compound 8 was obtained by hydrogenation of 7 using H2/Pd‐C. The IC50 values were calculated from displacement experiment of the radioligand [3H]WIN‐35,428 (2). 2′‐Aminococaine (8) showed high binding affinity to the DAT (14‐ and 1.3‐fold more active than cocaine and the radioligand 2, respectively). These results, along with previous results, emphasize the importance of a hydrogen‐bond donor group at the 2′‐position of cocaine to enhance binding affinity to the DAT.

中文翻译：

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可卡因的 2'-取代类似物：合成和多巴胺转运蛋白结合效力

制备了一系列 2'-取代的可卡因类似物 (4-8)，并在体外多巴胺转运蛋白 (DAT) 结合试验中进行了评估。在 Et3N 和苯的存在下，使用适当的酰氯通过酯化爱康宁甲酯 (3) 的 3β-羟基来制备化合物 4-7。通过使用 1N HCl 水解，从可卡因 (1) 中获得化合物 3，以提供爱康宁。HCl 使用被 HCl 气体饱和的甲醇进行酸催化酯化。使用 H2/Pd-C 将 7 加氢得到化合物 8。IC50 值是根据放射性配体 [3H] WIN-35,428 (2) 的位移实验计算得出的。2'-氨基可卡因 (8) 对 DAT 显示出高结合亲和力（分别比可卡因和放射性配体 2 的活性高 14 倍和 1.3 倍）。这些结果，连同之前的结果，