吡咯二酮酸衍生物作为 HIV-1 整合酶和逆转录酶核糖核酸酶 H 结构域双重抑制剂的构效关系。
Structure-activity relationship of pyrrolyl diketo acid derivatives as dual inhibitors of HIV-1 integrase and reverse transcriptase ribonuclease H domain.
机构信息
Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma , Rome, I-00185, Italy.
出版信息
J Med Chem. 2015 Feb 26;58(4):1915-28. doi: 10.1021/jm501799k. Epub 2015 Feb 11.
Abstract
The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well as therapeutic costs. HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets for HIV-1 chemotherapy, and the identification of dual IN/RNase H inhibitors is an attractive strategy for new drug development. We newly synthesized pyrrolyl derivatives that exhibited good potency against IN and a moderate inhibition of the RNase H function of RT, confirming the possibility of developing dual HIV-1 IN/RNase H inhibitors and obtaining new information for the further development of more effective dual HIV-1 inhibitors.
摘要
开发 HIV-1 双重抑制剂是一种极具创新性的方法，旨在降低药物的毒副作用和治疗成本。HIV-1 整合酶（IN）和逆转录酶相关核糖核酸酶 H（RNase H）都是 HIV-1 化学治疗的选择性靶标，而鉴定双重 IN/RNase H 抑制剂是开发新药的一种有吸引力的策略。我们新合成的吡咯衍生物对 IN 表现出良好的活性，对 RT 的 RNase H 功能有适度的抑制作用，证实了开发双重 HIV-1 IN/RNase H 抑制剂的可能性，并为进一步开发更有效的双重 HIV-1 抑制剂提供了新的信息。
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