Abstract：
The search for melatonin receptor agonists formed the main part of melatonin medicinal chemistry programs for the last three decades. In this short review, we summarize the two main aspects of these programs: the development of all the necessary tools to characterize the newly synthesized ligands at the two melatonin receptors MT1 and MT2, and the medicinal chemist\'s approaches to find chemically diverse ligands at these receptors. Both strategies are described. It turns out that the main source of tools were industrial laboratories, while the medicinal chemistry was mainly carried out in academia. Such complete accounts are interesting, as they delineate the spirits in which the teams were working demonstrating their strength and innovative character. Most of the programs were focused on nonselective agonists and few of them reached the market. In contrast, discovery of MT1-selective agonists and melatonergic antagonists with proven in vivo activity and MT1 or MT2-selectivity is still in its infancy, despite the considerable interest that subtype selective compounds may bring in the domain, as the physiological respective roles of the two subtypes of melatonin receptors, is still poorly understood. Poly-pharmacology applications and multitarget ligands have also been considered.
摘要：
在过去的三十年中，对褪黑激素受体激动剂的研究成为褪黑激素药物化学计划的主要部分。在这篇简短的评论中，我们总结了这些计划的两个主要方面：开发所有必要的工具来表征两种褪黑激素受体MT1和MT2上新合成的配体，以及药物化学家在这些受体上找到化学上不同的配体的方法。描述了这两种策略。原来工具的主要来源是工业实验室，而药物化学主要在学术界进行。如此完整的账户很有趣，他们描绘了团队工作的精神，展示了他们的力量和创新特征。大多数程序都集中在非选择性激动剂上，很少进入市场。相比之下,发现MT1选择性激动剂和褪黑素能拮抗剂，具有已证明的体内活性和MT1或MT2选择性仍处于起步阶段，尽管亚型选择性化合物可能会带来相当大的兴趣，作为褪黑激素受体的两种亚型的生理作用，仍然知之甚少。还考虑了多药理学应用和多靶配体。
