可逆型质子泵抑制剂最新研究进展-药学进展.pdfVIP

PROGRESS IN PHARMACEUTICAL SCIENCES 2016,40 6 :445-452 ( ) 445 可逆型质子泵抑制剂最新研究进展 黄群刚，朱启华，徐云根 * （中国药科大学药物化学教研室，江苏 南京 210009） + + [ 摘要 ] H /K -ATP 酶是胃酸分泌过程中的关键酶，质子泵抑制剂的问世虽然很大程度上提高了酸相关疾病患者的生活质量，但仍存在 酸不稳定性、起效慢、半衰期短、个体差异大等局限性。可逆型质子泵抑制剂通过竞争性抑制 H+/K +-ATP 酶的 K+ 结合位点，可以快速 持久地抑制胃酸分泌，有效改善不可逆质子泵抑制剂的种种缺陷。重点介绍了可逆型质子泵抑制剂的最新研究进展以及代表性药物的构 效关系和发现过程。 + + [ 关键词 ] H /K -ATP 酶；酸相关疾病；可逆型质子泵抑制剂；构效关系 [ 中图分类号 ] R975 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2016）06-0445-08 Research Advances in Reversible Proton Pump Inhibitors HUANG Qungang, ZHU Qihua, XU Yungen (Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China) + + [Abstract] H /K -ATPase plays an important role in the process of gastric acid secretion. Although proton pump inhibitors have considerably improved the quality of life for patients with acid related disorders, it still has many limitations, such as acid instability, slow onset, short half-life, large individual differences, etc.. Reversible proton pump inhibitors can inhibit gastric acid secretion with a fast onset of action in a potassium-competitive way and effectively overcome the shortcomings of irreversible proton pump inhibitors. This review introduced the progress in the research of reversible proton pump inhibitors and structure-activity relationships of representative drugs. + + [Key words] H /K -ATPase; acid related disorder; reversible proton pump inhibitor; structure-activity relationship acid related disorders ARD 脂溶性化合物，pKa 约为 4.0~5.0