Departamento de Química, Universidade Federal da Paraíba, Cidade Universitária, 58051-970, João Pessoa - PB, Brazil.
Eur J Med Chem. 2010 Apr;45(4):1508-14. doi: 10.1016/j.ejmech.2009.12.059. Epub 2010 Jan 13.
5-HT(1A) receptor antagonists have been employed to treat depression, but the lack of structural information on this receptor hampers the design of specific and selective ligands. In this study, we have performed CoMFA studies on a training set of arylpiperazines (high affinity 5-HT(1A) receptor ligands) and to produce an effective alignment of the data set, a pharmacophore model was produced using Galahad. A statistically significant model was obtained, indicating a good internal consistency and predictive ability for untested compounds. The information gathered from our receptor-independent pharmacophore hypothesis is in good agreement with results from independent studies using different approaches. Therefore, this work provides important insights on the chemical and structural basis involved in the molecular recognition of these compounds.
5-HT(1A) 受体拮抗剂已被用于治疗抑郁症，但由于缺乏该受体的结构信息，限制了特异性和选择性配体的设计。在这项研究中，我们对一组芳基哌嗪（高亲和力 5-HT(1A) 受体配体）进行了 CoMFA 研究，并使用 Galahad 生成了一个有效的数据集排列。得到了一个具有统计学意义的模型，表明对未测试化合物具有良好的内部一致性和预测能力。从我们与受体无关的药效基团假设中收集的信息与使用不同方法的独立研究的结果非常吻合。因此，这项工作为这些化合物的分子识别所涉及的化学和结构基础提供了重要的见解。
