H+/K+-ATPase (Proton Pump) is responsible for acid production from parietal cells of stomach. Acid-related disorders are caused by uncontrolled activity of proton pumps. Inhibition of these proton pumps has been shown to be effective in the treatment of GERD (Gastro-oesophageal reflux disease). Our aim was to investigate the effective proton pump inhibitor and prediction of the best analogues. Quantitative Structure Activity Relationship (QSAR) was performed on two sets of molecules, i.e., on tert-Butyl1, 5- bis(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-1,5-dioxopentan-2-ylcarbamte urea/thio-urea derivatives and schiff base of quinazolinone derivatives. Biological activity for H+/K+-ATPase inhibition was found to be significantly correlated with polarizability and surface tension (ST) for the first set of analogues and with polar surface area (PSA), polarizability and hydrophobic constant for the second set of analogues, indicating the involvement of strong electronic interaction between the molecule and the receptor. Based on the correlations obtained from the schiff’s base derivatives by the QSAR model, new H+/K+-ATPase inhibitors were predicted. Based on the generated QSAR Model, a series of new compounds were designed. Afterwards, these compounds were docked with the protein and their ADME properties were evaluated. Toxicity of these new analogues was also predicted. The QSAR studies were not performed on both sets of analogues previously. Present study predicts more potent, less toxic, easily synthesisable leadcompounds.

H+/K+-ATPase（质子泵）负责胃壁细胞产酸。与酸相关的疾病是由不受控制的质子泵活动引起的。已证明抑制这些质子泵可有效治疗 GERD（胃食管反流病）。我们的目标是研究有效的质子泵抑制剂和最佳类似物的预测。对两组分子进行定量结构活性关系 (QSAR)，即， 关于叔丁基1, 5-双(4-(苯并[d]异噻唑-3-基)哌嗪-1-基)-1,5-二氧戊烷-2-基氨基甲酸酯脲/硫脲衍生物和喹唑啉酮衍生物的席夫碱. 发现 H+/K+-ATPase 抑制的生物活性与第一组类似物的极化率和表面张力 (ST) 以及第二组类似物的极性表面积 (PSA)、极化率和疏水常数显着相关，表明分子和受体之间存在强电子相互作用。根据 QSAR 模型从希夫碱导数获得的相关性，预测了新的 H+/K+-ATPase 抑制剂。基于生成的 QSAR 模型，设计了一系列新化合物。然后，将这些化合物与蛋白质对接并评估它们的 ADME 特性。还预测了这些新类似物的毒性。之前没有对两组类似物进行 QSAR 研究。目前的研究预测了更有效、毒性更小、易于合成的铅化合物。