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治疗痛风的药物:最新进展与未来展望。

Agents for the Treatment of Gout: Current Advances and Future Perspectives.

机构信息

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.

出版信息

J Med Chem. 2023 Nov 9;66(21):14474-14493. doi: 10.1021/acs.jmedchem.3c01710. Epub 2023 Oct 31.

Abstract

Gout is characterized by hyperuricemia and the deposition of monosodium urate (MSU) crystals around joints. Despite the availability of several drugs on the market, its treatment remains challenging owing to the notable side effects, such as hepatorenal toxicity and cardiovascular complications, that are associated with most existing agents. This perspective aims to summarize the current research progress in the development of antigout agents, particularly focusing on xanthine oxidase (XO) and urate anion transporter 1 (URAT1) inhibitors from a medicinal chemistry viewpoint and their preliminary structure-activity relationships (SARs). This perspective provides valuable insights and theoretical guidance to medicinal chemists for the discovery of antigout agents with novel chemical structures, better efficiency, and lower toxicity.

摘要

痛风的特征是血尿酸水平升高和单钠尿酸盐(MSU)晶体在关节周围沉积。尽管市场上有几种药物,但由于大多数现有药物都存在肝肾功能毒性和心血管并发症等显著副作用,其治疗仍然具有挑战性。本综述旨在从药物化学的角度总结目前在抗痛风药物开发方面的研究进展,特别关注黄嘌呤氧化酶(XO)和尿酸阴离子转运蛋白 1(URAT1)抑制剂,并对其初步的构效关系(SAR)进行总结。本综述为药物化学家提供了有价值的见解和理论指导,有助于发现具有新型化学结构、更高效率和更低毒性的抗痛风药物。

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