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含三唑的杂合体与抗潜能 - 第 I 部分:1,2,3-三唑。

Triazole-containing hybrids with anti- potential - Part I: 1,2,3-Triazole.

机构信息

Guangdong Xianqiang Pharmaceutical Co., Ltd, Guangzhou, PR China.

Guangdong Zhongsheng Pharmaceutical Co., Ltd, Dongguan, Guangdong, PR China.

出版信息

Future Med Chem. 2021 Apr;13(7):643-662. doi: 10.4155/fmc-2020-0301. Epub 2021 Feb 23.

Abstract

Tuberculosis regimens currently applied in clinical practice require months of multidrug therapy, which imposes a major challenge of patient compliance and drug resistance development. Moreover, because of the increasing emergence of hard-to-treat tuberculosis, this disease continues to be a significant threat to the human population. 1,2,3-triazole as a privileged structure has been widely used as an effective template for drug discovery, and 1,2,3-triazole-containing hybrids that can simultaneously act on dual or multiple targets in  have the potential to circumvent drug resistance, enhance efficacy, reduce side effects and improve pharmacokinetic as well as pharmacodynamic profiles. Thus, 1,2,3-triazole-containing hybrids are useful scaffolds for the development of antitubercular agents. This review aims to highlight recent advances of 1,2,3-triazole-containing hybrids with potential activity against various forms of , covering articles published between 2015 and 2020. The structure-activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective drug candidates.

摘要

目前在临床实践中应用的结核病方案需要数月的多药治疗,这给患者的依从性和耐药性发展带来了重大挑战。此外,由于难以治疗的结核病不断出现,这种疾病仍然对人类构成重大威胁。1,2,3-三唑作为一种特权结构,已被广泛用作药物发现的有效模板,而同时能针对双重或多种目标发挥作用的 1,2,3-三唑类混合物有可能规避耐药性、提高疗效、降低副作用,并改善药代动力学和药效学特征。因此,含 1,2,3-三唑的混合物是开发抗结核药物的有用支架。本综述旨在重点介绍 2015 年至 2020 年期间发表的具有针对各种形式的潜在活性的含 1,2,3-三唑的混合物的最新进展。还讨论了结构-活性关系和作用机制,以促进更有效的候选药物的进一步合理设计。

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