Li Junyi, Ye Bing, Gao Shenghua, Liu Xinyong, Zhan Peng
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.
Expert Opin Drug Discov. 2024 Dec;19(12):1439-1456. doi: 10.1080/17460441.2024.2415309. Epub 2024 Oct 13.
This review encapsulates the recent strides in the development of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment, focusing on the novel structural designs that promise to overcome limitations of existing therapies, such as drug resistance and toxicity.
We underscore the application of computational chemistry and structure-based drug design in refining NNRTIs with enhanced potency and safety.
Highlighting the emergence of diverse chemical scaffolds like diarylpyrimidines, indoles, DABOs and HEPTs, the review reveals compounds with nanomolar efficacy and improved pharmacokinetics. The integration of artificial intelligence in drug discovery is poised to accelerate the evolution of NNRTIs, laying the foundation for addressing drug resistance in the era of anti-HIV therapy through innovative designs and multi-target strategies.
本综述总结了用于治疗艾滋病的非核苷类逆转录酶抑制剂（NNRTIs）的最新进展，重点关注有望克服现有疗法局限性（如耐药性和毒性）的新型结构设计。
我们强调了计算化学和基于结构的药物设计在优化具有更高效力和安全性的NNRTIs方面的应用。
该综述突出了二芳基嘧啶、吲哚、二氮杂双环辛烷和庚烷等多种化学骨架的出现，揭示了具有纳摩尔效力和改善药代动力学的化合物。人工智能在药物发现中的整合有望加速NNRTIs的发展，为通过创新设计和多靶点策略解决抗艾滋病治疗时代的耐药性问题奠定基础。
