Laboratory of Pharmaceutical Design & Synthesis, College of Sciences, Northwest A&F University, Yangling, P. R. China.
Mini Rev Med Chem. 2010 Jan;10(1):62-72. doi: 10.2174/138955710791112578.
Since the first case of acquired immunodeficiency syndrome (AIDS) was reported in 1981, AIDS, as the global disease affecting 33.2 million people in 2007, has always been an unsolved problem worldwide. Reverse transcriptase (RT) is a crucial enzyme in the life cycle of human immunodeficiency virus type 1 (HIV-1), and thereby has been the prime drugs target for antiretroviral (ARV) therapy against AIDS. To date, two classes of RT inhibitors (RTIs), e.g., nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), and a lot of compounds tested as RTIs have been described. To our knowledge, bis(heteroaryl)piperazines (BHAPs) have been considered as one class of promising NNRTIs, such as structurally and chemically related NNRTI delavirdine, which was approved by the U. S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection in 1997. In this mini-review, we make attempts to report the progress of synthesis and structure-activity relationship (SAR) of BHAPs, in the meantime, the synergistic inhibition of HIV-1 replication by combining delavirdine with other HIV-1 inhibitors is also discussed. It will pave the way for the design and development of BHAPs as anti-HIV-1 agents in AIDS chemotherapy in the future.
自 1981 年首例获得性免疫缺陷综合征（AIDS）病例报告以来，艾滋病作为全球影响 2007 年 3320 万人的疾病，一直是全球尚未解决的问题。逆转录酶（RT）是人类免疫缺陷病毒 1（HIV-1）生命周期中的关键酶，因此一直是抗逆转录病毒（ARV）治疗艾滋病的主要药物靶点。迄今为止，已经描述了两类 RT 抑制剂（RTIs），例如核苷逆转录酶抑制剂（NRTIs）和非核苷逆转录酶抑制剂（NNRTIs），以及许多作为 RTIs 测试的化合物。据我们所知，双（杂芳基）哌嗪（BHAPs）已被认为是一类有前途的 NNRTIs，如结构和化学上相关的 NNRTI 地拉韦啶，它于 1997 年被美国食品和药物管理局（FDA）批准用于治疗 HIV-1 感染。在这篇综述中，我们尝试报告 BHAPs 的合成和构效关系（SAR）的进展，同时还讨论了将地拉韦啶与其他 HIV-1 抑制剂联合使用对 HIV-1 复制的协同抑制作用。这将为未来艾滋病化疗中设计和开发 BHAPs 作为抗 HIV-1 药物铺平道路。
