With the aim to discover a novel potent potassium-competitive acid blocker (P-CAB) agent, a series of 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4–c]pyrazole derivatives were synthesized, and their H⁺/K⁺-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 3′-((3-(2-fluorophenyl)-5-methyl-5,6-dihydropyrrolo[3,4–c]pyrazol-2(4H)-yl)methyl)-[1,1′-biphenyl]-3-carboxamide not only exhibited potent H⁺/K⁺-ATPase inhibitory activity but olso showed potent inhibitory action in vivo on histamine-stimulated gastric acid secretion. In addition, the lead compound displayed favourable oral pharmacokinetic properties in rats, which was worthy of further study as a novel P-CAB agent.

为了发现一种新型强效钾竞争性酸阻滞剂 (P-CAB)，合成了一系列 5-甲基-2,4,5,6-四氢吡咯并[3,4- c ]吡唑衍生物，并对其评价H ⁺ /K ⁺ -ATP酶抑制活性和对大鼠组胺刺激的胃酸分泌的抑制作用。在合成的化合物中，化合物3'-((3-(2-氟苯基)-5-甲基-5,6-二氢吡咯并[3,4- c ]吡唑-2(4H)-基)甲基)-[1, 1'-联苯]-3-甲酰胺不仅表现出有效的H ⁺ /K ⁺ -ATPase抑制活性，而且在体内也表现出有效的抑制作用关于组胺刺激的胃酸分泌。此外，该先导化合物在大鼠中表现出良好的口服药代动力学特性，作为一种新型 P-CAB 药物值得进一步研究。