Guariento Sara, Franchini Silvia, Tonelli Michele, Fossa Paola, Sorbi Claudia, Cichero Elena, Brasili Livio
a Department of Pharmacy , University of Genoa , Genoa , Italy.
b Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):214-230. doi: 10.1080/14756366.2016.1247057.
The 5-hydroxytryptamine (5-HT) receptors represent an attractive target in drug discovery. In particular, 5-HT agonists and partial agonists are deeply investigated for their potential role in the treatment of anxiety, depression, ischaemic brain disorder and more recently, of pain. On the other hand, 5-HT antagonists have been revealed promising compounds in cognition disorders and, lately, in cancer. Thus, the discovery of 5HT ligands is nowadays an appealing research activity in medicinal chemistry. In this work, Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) were applied on an in-house library of 5-HT ligands bearing different chemical scaffolds in order to elucidate their affinity and selectivity for the target Following this procedure, a number of structural modifications have been drawn for the development of much more effective 5-HTR ligands. [Formula: see text].
5-羟色胺（5-HT）受体是药物研发中一个具有吸引力的靶点。特别是，5-HT激动剂和部分激动剂因其在治疗焦虑、抑郁、缺血性脑疾病以及最近在疼痛治疗中的潜在作用而受到深入研究。另一方面，5-HT拮抗剂在认知障碍以及最近在癌症治疗中已被证明是有前景的化合物。因此，如今发现5-HT配体是药物化学中一项有吸引力的研究活动。在这项工作中，比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）被应用于一个内部的5-HT配体库，这些配体具有不同的化学支架，以阐明它们对靶点的亲和力和选择性。按照这个程序，已经为开发更有效的5-HTR配体进行了一些结构修饰。[公式：见正文]
