Medicinal Chemistry, SAR, and Molecular Insights Into 2,4-Thiazolidinediones as Antidiabetic Agents (2020–2025)

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Neeru Malik, Rajesh Kumar Singh
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引用次数: 0

Abstract

The thiazolidinedione (TZD) scaffold has long been recognized for its pharmacological versatility, particularly in the treatment of metabolic and inflammatory disorders. Among its derivatives, 2,4-thiazolidinediones (2,4-TZDs) have emerged as a prominent class of antidiabetic agents with diverse molecular targets. While their role as peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists is well established, recent studies have revealed additional therapeutic mechanisms, including inhibition of protein tyrosine phosphatase 1B (PTP-1B), α-amylase, α-glucosidase, and aldose reductase—each contributing to improved glucose regulation and diabetes management. Moreover, the rise of dual and multitarget inhibitors highlights the evolving therapeutic potential of 2,4-TZDs beyond conventional pathways. This review presents a comprehensive analysis of recent developments (2020–2025) in the medicinal chemistry, structure–activity relationships (SARs), and antidiabetic mechanisms of 2,4-TZDs. Key structural modifications and their influence on biological activity are critically evaluated, alongside updates on recent patent disclosures and ongoing clinical trials. By integrating medicinal chemistry insights with pharmacological data, this review aims to support the rational design of next-generation 2,4-TZD-based antidiabetic therapeutics.

Abstract Image

2,4-噻唑烷二酮类抗糖尿病药物的药物化学、SAR和分子研究(2020-2025)
噻唑烷二酮(TZD)支架长期以来一直被认为具有药理上的多功能性,特别是在治疗代谢和炎症性疾病方面。在其衍生物中,2,4-噻唑烷二酮(2,4- tzds)已成为一类突出的抗糖尿病药物,具有不同的分子靶点。虽然它们作为过氧化物酶体增殖物激活受体γ (PPAR-γ)激动剂的作用已经得到了很好的证实,但最近的研究揭示了其他的治疗机制,包括抑制蛋白酪氨酸磷酸酶1B (PTP-1B)、α-淀粉酶、α-葡萄糖苷酶和醛糖还原酶,它们都有助于改善葡萄糖调节和糖尿病管理。此外,双靶点和多靶点抑制剂的兴起凸显了2,4- tzd在传统途径之外不断发展的治疗潜力。本文综述了2,4- tzds在药物化学、构效关系(SARs)和抗糖尿病机制方面的最新进展(2020-2025)。关键的结构修饰及其对生物活性的影响进行了严格评估,同时对最近的专利披露和正在进行的临床试验进行了更新。通过将药物化学见解与药理学数据相结合,本综述旨在支持基于2,4- tzd的下一代降糖药物的合理设计。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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