Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, S.G. Highway, Chharodi, Ahmedabad, 382 481, Gujarat, India.
Med Chem. 2013 Mar;9(2):222-39. doi: 10.2174/1573406411309020007.
QSAR study was performed on a series of aryl carboxylic acid amide derivatives (62 analogs) to establish structural features required for human dihydroorotate dehydrogenase (hDHODH) inhibition. Statistical significant QSAR models were developed for the prediction of hDHODH inhibitory activity by applying MLR analysis (r2 = 0.851 and q2 = 0.795), PCR analysis (r2 = 0.713 and q2 = 0.667) and PLS analysis (r2 = 0.848 and q2 = 0.802). QSAR study emphasized the importance of topological, estate number, hydrophobic and alignment independent descriptors for the prediction of hDHODH inhibitory activity. SaasCcount descriptor suggested the presence of carbon atoms in five member aryl ring system. Positive impact of alignment independent descriptors reveals the presence of carbonyl oxygen and chloro group in this series of compounds. DistTopo signifies basic connectivity of atoms in the molecules. High degree of predictability of the proposed QSAR models offers a great potential for the design and development of potent hDHODH inhibitors.
QSAR 研究对一系列芳基羧酸酰胺衍生物（62 个类似物）进行了研究，以确定抑制人二氢乳清酸脱氢酶（hDHODH）所需的结构特征。通过应用 MLR 分析（r2 = 0.851，q2 = 0.795）、PCR 分析（r2 = 0.713，q2 = 0.667）和 PLS 分析（r2 = 0.848，q2 = 0.802），为预测 hDHODH 抑制活性开发了具有统计学意义的 QSAR 模型。QSAR 研究强调拓扑、电子数、疏水性和独立于排列的描述符对于预测 hDHODH 抑制活性的重要性。SaasCcount 描述符表明五员芳环系统中存在碳原子。独立于排列的描述符的积极影响表明该系列化合物中存在羰基氧和氯基团。DistTopo 表示分子中原子的基本连接性。所提出的 QSAR 模型具有高度的可预测性，为设计和开发有效的 hDHODH 抑制剂提供了巨大潜力。
