哒嗪作为药物化学中抗癌剂的特殊支架的最新贡献:最新综述

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-07-28 DOI:10.1016/j.bmc.2024.117847
Zi-Qiang Liu , Qian Zhang , Yu-Lin Liu , Xiao-Qian Yu , Rui-Hao Chui , Lin-Lin Zhang , Bing Zhao , Li-Ying Ma
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引用次数: 0

摘要

哒嗪作为一种特殊的支架,因其多种生物活性而被广泛用于药物开发。特别是围绕其独特的抗癌特性,人们合成并评估了大量含哒嗪的化合物,这些化合物针对的是癌症发生和发展过程中的各种生物过程。这些化合物包括谷氨酰胺酶 1(GLS1)抑制剂、肌球蛋白受体激酶(TRK)抑制剂和含溴结构域蛋白(BRD)抑制剂,分别针对异常的肿瘤代谢、细胞信号传导和表观遗传修饰。在上述药物中,哒嗪类药物既可作为核心框架,也可作为弹头,在癌症治疗中具有广阔的应用前景。因此,本综述旨在总结 2020 年至 2024 年期间哒嗪衍生物作为强效抗癌药物的最新贡献,主要侧重于其结构-活性关系(SAR)和开发策略,以期说明不同药物化学家对哒嗪支架的应用为抗癌药物的合理设计提供了新的见解。
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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Recent contributions of pyridazine as a privileged scaffold of anticancer agents in medicinal chemistry: An updated review

Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure–activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs.

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CiteScore
7.20
自引率
4.30%
发文量
567
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