Calogeropoulou Theodora, Detsi Anastasia, Lekkas Eleni, Koufaki Maria
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, 48 Vas. Constantinou Avenue, 11635 Athens, Greece.
Curr Top Med Chem. 2003;3(13):1467-95. doi: 10.2174/1568026033451763.
Control of AIDS requires development of special therapeutic strategies in order to reduce the level of monocyte/macrophage HIV infection, to prevent spread of HIV within the monocyte/macrophage reservoir, to maintain a therapeutically effective drug concentration in sanctuaries such as the brain and to overcome the problem of cellular resistance mechanisms. A popular approach towards this end has been the development of prodrugs of anti-HIV drugs. This review covers the different strategies devised for the design of prodrugs of anti-HIV agents with emphasis on the recent findings in this field of research. Thus, prodrugs of nucleoside reverse transcriptase inhibitors (NRTIs) including, 5'-O carboxylic ester derivatives, 5'-O- monophosphate analogues, macromolecular derivatives, prodrugs of purine nucleosides, prodrugs of acyclic nucleosides, homo and hetero dinucleotides, prodrugs of non-classical nucleoside analogues, boranophosphate triesters of NRTIs, and prodrugs of protease inhibitors including acyl-substituted prodrugs, prodrugs with increased water solubility, monophosphate prodrugs, and conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor through spontaneously cleavable linkers, constitute the subject of this review.
控制艾滋病需要制定特殊的治疗策略，以降低单核细胞/巨噬细胞感染HIV的水平，防止HIV在单核细胞/巨噬细胞储存库中传播，在脑等庇护所维持治疗有效的药物浓度，并克服细胞耐药机制问题。为此，一种常用的方法是开发抗HIV药物的前药。本综述涵盖了为设计抗HIV药物前药而制定的不同策略，重点是该研究领域的最新发现。因此，核苷类逆转录酶抑制剂（NRTIs）的前药，包括5'-O羧酸酯衍生物、5'-O-单磷酸类似物、大分子衍生物、嘌呤核苷前药、无环核苷前药、同型和异型二核苷酸、非经典核苷类似物前药、NRTIs的硼磷酸三酯，以及蛋白酶抑制剂的前药，包括酰基取代前药、水溶性增加的前药、单磷酸前药，以及通过可自发裂解的连接子与逆转录酶抑制剂结合的HIV蛋白酶抑制剂，构成了本综述的主题。
