Diuretics are the first-line therapy for widespread cardiovascular and non-cardiovascular diseases. Traditional diuretics are commonly prescribed for treatment in patients with hypertension, edema and heart failure, as well as with a number of kidney problems. They are diseases with high mortality, and the number of patients suffering from heart and kidney diseases is increasing year by year. The use of several classes of diuretics currently available for clinical use exhibits an overall favorable risk/benefit balance. However, they are not devoid of side effects. Hence, pharmaceutical researchers have been making efforts to develop new drugs with a better pharmacological profile. High-throughput screening, progress in protein structure analysis and modern methods of chemical modification have opened good possibilities for identification of new promising agents for preclinical and clinical testing. In this review, we provide an overview of the medicinal chemistry approaches toward the development of small molecule compounds showing diuretic activity that have been discovered over the past decade and are interesting drug candidates. We have discussed promising natriuretics/aquaretics/osmotic diuretics from such classes as: vasopressin receptor antagonists, SGLT2 inhibitors, urea transporters inhibitors, aquaporin antagonists, adenosine receptor antagonists, natriuretic peptide receptor agonists, ROMK inhibitors, WNK‐SPAK inhibitors, and pendrin inhibitors.

利尿剂是广泛的心血管和非心血管疾病的一线治疗。传统的利尿剂通常被处方用于高血压，浮肿和心力衰竭以及许多肾脏疾病患者的治疗。它们是高死亡率的疾病，患有心脏和肾脏疾病的患者人数逐年增加。当前可用于临床的几种利尿剂的使用表现出总体有利的风险/益处平衡。但是，它们并非没有副作用。因此，药物研究人员一直在努力开发具有更好药理学特性的新药。高通量筛选 蛋白质结构分析和现代化学修饰方法的进步为鉴定临床前和临床测试中新的有希望的药物提供了良好的可能性。在这篇综述中，我们概述了开发具有利尿活性的小分子化合物的药用化学方法，这些化合物在过去十年中被发现并且是​​有趣的候选药物。我们已经讨论了有前景的利尿剂/水生植物/渗透性利尿剂，例如：加压素受体拮抗剂，SGLT2抑制剂，尿素转运蛋白抑制剂，水通道蛋白拮抗剂，腺苷受体拮抗剂，利钠肽受体激动剂，ROMK抑制剂，WNK-SPAK抑制剂和pendrin抑制剂。我们概述了开发具有利尿作用的小分子化合物的药用化学方法，这些化合物在过去十年中被发现并且是​​有趣的候选药物。我们已经讨论了有前景的利尿剂/水生植物/渗透性利尿剂，例如：加压素受体拮抗剂，SGLT2抑制剂，尿素转运蛋白抑制剂，水通道蛋白拮抗剂，腺苷受体拮抗剂，利钠肽受体激动剂，ROMK抑制剂，WNK-SPAK抑制剂和pendrin抑制剂。我们概述了开发具有利尿作用的小分子化合物的药用化学方法，这些化合物在过去十年中被发现并且是​​有趣的候选药物。我们已经讨论了有前景的利尿剂/水生植物/渗透性利尿剂，它们包括：血管加压素受体拮抗剂，SGLT2抑制剂，尿素转运蛋白抑制剂，水通道蛋白拮抗剂，腺苷受体拮抗剂，利尿钠肽受体激动剂，ROMK抑制剂，WNK-SPAK抑制剂和pendrin抑制剂。