The Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS), one of the most perilous diseases known to humankind. A 2023 estimate put the number of people living with HIV around 40 million worldwide, with the majority benefiting from various antiretroviral therapies. Consequently, the urgent need for the development of effective drugs to combat this virus cannot be overstated. In the realm of medicinal and organic chemistry, the synthesis and identification of novel compounds capable of inhibiting HIV enzymes at different stages of their life cycle are of paramount importance.

Notably, the spotlight is on the progress made in enhancing the potency of HIV inhibitors through the use of piperazine-based compounds. Multiple studies have revealed that the incorporation of a piperazine moiety results in a noteworthy enhancement of anti-HIV activity. The piperazine ring assumes a pivotal role in shaping the pharmacophore responsible for inhibiting HIV-1 at critical stage, including attachment, reverse transcription, integration, and protease activity. This review also sheds light on the various opportunities that can be exploited to develop effective antiretroviral targets and eliminate latent HIV reservoirs. The advancement of highly potent analogues in HIV inhibitor research has been greatly facilitated by contemporary medicinal strategies, including molecular/fragment hybridization, structure-based drug design, and bioisosterism. These techniques have opened up new avenues for the development of compounds with enhanced efficacy in combating the virus.

人类免疫缺陷病毒（HIV）是获得性免疫缺陷综合症（AIDS）的病原体，艾滋病是人类已知的最危险的疾病之一。据估计，到 2023 年，全球艾滋病毒感染者人数约为 4000 万，其中大多数受益于各种抗逆转录病毒疗法。因此，开发有效药物来对抗这种病毒的迫切需要怎么强调也不为过。在药物和有机化学领域，合成和鉴定能够在生命周期的不同阶段抑制 HIV 酶的新型化合物至关重要。

值得注意的是，人们关注的焦点是通过使用基于哌嗪的化合物来增强艾滋病毒抑制剂的效力所取得的进展。多项研究表明，哌嗪部分的掺入可显着增强抗 HIV 活性。哌嗪环在塑造药效团方面发挥着关键作用，药效团负责在关键阶段抑制 HIV-1，包括附着、逆转录、整合和蛋白酶活性。这篇综述还揭示了可用于开发有效的抗逆转录病毒靶标和消除潜在艾滋病毒储存库的各种机会。当代医学策略，包括分子/片段杂交、基于结构的药物设计和生物等排现象，极大地促进了 HIV 抑制剂研究中高效类似物的进步。这些技术为开发具有增强抗病毒功效的化合物开辟了新途径。