Zhang Kun, Zhang Yu-Jie, Li Min, Pannecouque Christophe, De Clercq Erik, Wang Shuai, Chen Fen-Er
Department of Chemistry, Engineering Center of Catalysis and Synthesis for Chiral Molecules, Fudan University, Shanghai, China.
Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, China.
Med Res Rev. 2025 Mar;45(2):426-483. doi: 10.1002/med.22080. Epub 2024 Aug 26.
The pivotal involvement of reverse transcriptase activity in the pathogenesis of the progressive HIV virus has stimulated gradual advancements in drug discovery initiatives spanning three decades. Consequently, nonnucleoside reverse transcriptase inhibitors (NNRTIs) have emerged as a preeminent category of therapeutic agents for HIV management. Academic institutions and pharmaceutical companies have developed numerous NNRTIs, an essential component of antiretroviral therapy. Six NNRTIs have received Food and Drug Administration approval and are widely used in clinical practice, significantly improving the quality of HIV patients. However, the rapid emergence of drug resistance has limited the effectiveness of these medications, underscoring the necessity for perpetual research and development of novel therapeutic alternatives. To supplement the existing literatures on NNRTIs, a comprehensive review has been compiled to synthesize this extensive dataset into a comprehensible format for the medicinal chemistry community. In this review, a thorough investigation and meticulous analysis were conducted on the progressions achieved in NNRTIs within the past 8 years (2016-2023), and the experiences and insights gained in the development of inhibitors with varying chemical structures were also summarized. The provision of a crucial point of reference for the development of wide-ranging anti-HIV medications is anticipated.
逆转录酶活性在进行性艾滋病毒发病机制中的关键作用推动了三十年来药物研发工作的逐步进展。因此，非核苷类逆转录酶抑制剂（NNRTIs）已成为治疗艾滋病毒的一类卓越治疗药物。学术机构和制药公司已开发出众多NNRTIs，它们是抗逆转录病毒疗法的重要组成部分。六种NNRTIs已获得美国食品药品监督管理局批准并广泛应用于临床实践，显著提高了艾滋病毒患者的生活质量。然而，耐药性的迅速出现限制了这些药物的有效性，凸显了持续研发新型治疗方案的必要性。为补充现有关于NNRTIs的文献，已编写了一篇全面综述，将这一广泛的数据集整合为一种可供药物化学界理解的形式。在本综述中，对过去8年（2016 - 2023年）NNRTIs取得的进展进行了深入研究和细致分析，并总结了开发具有不同化学结构抑制剂所获得的经验和见解。预计可为广泛的抗艾滋病毒药物研发提供关键参考点。
