In our pursuit of developing a novel and potent potassium-competitive acid blocker (P-CAB), we synthesized pyrrole derivatives focusing on compounds with low log D and high ligand-lipophilicity efficiency (LLE) values. Among the compounds synthesized, the compound 13e exhibited potent H⁺,K⁺-ATPase inhibitory activity and potent gastric acid secretion inhibitory action in vivo. Its maximum efficacy was more potent and its duration of action was much longer than those of proton pump inhibitors (PPIs). Therefore, compound 13e (1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate, TAK-438) was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases.

中文翻译：

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发现一种新型吡咯衍生物1- [5-（2-氟苯基）-1-（吡啶-3-基磺酰基）-1 H-吡咯-3-基] -N-甲基甲胺富马酸酯（TAK-438），作为钾-竞争性阻酸剂（P-CAB）

在我们寻求开发新型有效的钾竞争性酸阻滞剂（P-CAB）的过程中，我们合成了吡咯衍生物，重点关注具有低log D和高配体亲脂性（LLE）值的化合物 。在合成的化合物中，化合物13e在体内表现出有效的H ⁺，K ⁺ -ATP酶抑制活性和有效的胃酸分泌抑制作用。与质子泵抑制剂（PPI）相比，它的最大功效更强，作用时间更长。因此，化合物13e（1- [5-（2-氟苯基）-1-（吡啶-3-基磺酰基）-1 H-吡咯-3-基] -N-富马酸甲基甲胺胺（TAK-438）被选为治疗胃食管反流病（GERD），消化性溃疡和其他与酸有关的疾病的药物候选物。