IBMC, Department of Biochemistry, Faculty of Pharmacy, University of Porto, 4150-047 Porto, Portugal.
Eur J Med Chem. 2009 Dec;44(12):5045-54. doi: 10.1016/j.ejmech.2009.09.008. Epub 2009 Sep 18.
The multiobjective optimization technique based on the desirability estimation of several interrelated responses (MOOP-DESIRE) has been recently applied to quantitative structure-activity relationship (QSAR) studies. However, the advantage of applying this new methodology to the study of selectivity and affinity to competitive targets has been little explored. We used the MOOP-DESIRE methodology and a variation of this, to study the arylpiperazine derivates that could interact with 5-HT(1A) and 5-HT(2A), serotonin receptor subtypes with the objective of designing more selective molecules for the 5-HT(1A) receptor. We did show that the model results are in agreement with the available pharmacophore descriptions, guaranteeing an appropriate structural correlation and proving the methodology, as a useful tool for the important problem of selective drug design.
基于对多个相关响应的理想评估的多目标优化技术（MOOP-DESIRE）最近已被应用于定量构效关系（QSAR）研究中。然而，应用这种新方法研究选择性和亲和力对竞争性靶标的优势尚未得到充分探索。我们使用 MOOP-DESIRE 方法及其变体研究了可以与 5-HT（1A）和 5-HT（2A）相互作用的芳基哌嗪衍生物，这些受体亚型是血清素受体，目的是设计对 5-HT（1A）受体更具选择性的分子。我们确实表明，模型结果与现有的药效团描述一致，保证了适当的结构相关性，并证明了该方法作为选择性药物设计这一重要问题的有用工具。
