Recent discoveries in HIV-1 reverse transcriptase inhibitors

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Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1

GW4511, GW4751, and GW3011 showed IC50 values < or =2 nM against wild type HIV-1 and <10 nM against 16 mutants. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. The antiviral data together with the favorable pharmacokinetic data of GW4511 suggested that these benzophenones possess attributes of a new NNRTI drug candidate.     

二芳基胺类HIV-1非核苷类逆转录酶抑制剂研究进展

开发新型具有高效抗耐药性及良好药动学性质的非核苷类逆转录酶抑制剂（NNRTIs）依然是目前抗艾滋病药物研究领域迫切需要解决的科研问题。NNRTIs呈现结构多样性,但是其药效团却具有很大的相似性,不同类型的NNRTIs分子中往往存在共同或相近的骨架体系——优势结构。近年来被广泛研究的二芳基嘧啶类、二苯基唑类和“杂环-NH-取代苯”类NNRTIs分子中均存在二芳基胺（U—Het—NH-PhX）这一优势结构,虽然这3类抑制剂研发过程不同,但它们的研发历程对以优势结构为导向的NNRTIs骨架变换及取代基优化具有重要的指导意义。本文综述了含有二芳基胺优势结构的NNRTIs的研究进展。     

The QSAR analysis of tricyclic non-nucleoside inhibitors of HIV-1 reverse transcriptase

The inhibitory activities against HIV-1 RT of 44 tricyclic oxazepinones (from ref. 8, 9, 12) and 76 tricyclic diazepinones (from ref. 10, 11) have been correlated with 15 physicochemical parameters. The physicochemical parameters and 3D models of investigated compounds were obtained with the HyperChem program. A correlation between biological activity data (from ref. 8-12) and physicochemical data of the examined compounds was investigated by the regression analysis method with the STATISTICA program.