Structure-Activity Relationships of Synthetic Cathinones.
Structure-Activity Relationships of Synthetic Cathinones.
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DOI：
10.1007/7854_2016_41
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发表时间：
2017
影响因子：
--
通讯作者：
Dukat M
中科院分区：
文献类型：
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作者：
Glennon RA;Dukat M
直到最近，人们对卡西酮类似物的结构-活性关系（SAR）兴趣不大，因为可用的药物很少，而且它们代表了相对较小的药物滥用问题。大多数早期SAR是基于使用啮齿动物的行为（例如运动和药物辨别）研究制定的。随着在过去几年中大量新的卡西酮类似物（称为“合成卡西酮”）在秘密市场上的出现，以及认识到它们可能作为释放剂作用于多巴胺、去甲肾上腺素和/或5-羟色胺转运蛋白（即，作为底物）或再摄取抑制剂（即，作为转运阻滞剂），现在已经能够以更有效和更系统的方式更好地检查其SAR，甚至其定量SAR（QSAR）。SAR图像开始出现，并且发现关键结构特征，例如末端胺的性质、α取代基的大小、立体化学以及芳族取代基的存在和位置，都会影响作用（即，作为释放剂或再摄取抑制剂）和转运蛋白选择性。
Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available, and because they represented a relatively minor drug abuse problem. Most of the early SAR was formulated on the basis of behavioral (e.g. locomotor and drug discrimination) studies using rodents. With the emergence on the clandestine market in the last few years of a large number of new cathinone analogs, termed “synthetic cathinones”, and the realization that they likely act at dopamine, norepinephrine, and/or serotonin transporters as releasing agents (i.e., as substrates) or reuptake inhibitors (i.e., as transport blockers), it has now become possible to better examine their SAR, and even their quantitative SAR (QSAR), in a more effective and systematic manner. An SAR picture is beginning to emerge and key structural features, such as the nature of the terminal amine, the size of the α substituent, stereochemistry, and the presence and position of aromatic substituents, are being found to impact action (i.e., as releasing agents or reuptake inhibitors) and transporter selectivity.