吡咯芳基砜（PAS）衍生物的抗HIV-1活性：吡咯核2位新型酯类和酰胺类化合物的合成及构效关系研究

Anti-HIV-1 activity of pyrryl aryl sulfone (PAS) derivatives: synthesis and SAR studies of novel esters and amides at the position 2 of the pyrrole nucleus.

作者信息

Silvestri Romano, Artico Marino, La Regina Giuseppe, De Martino Gabriella, La Colla Massimiliano, Loddo Roberta, La Colla Paolo

机构信息

Dipartimento di Studi Farmaceutici, Università di Roma "La Sapienza", Piazzale Aldo Moro 5, Rome 00185, Italy.

出版信息

Farmaco. 2004 Mar;59(3):201-10. doi: 10.1016/j.farmac.2003.11.004.

DOI:10.1016/j.farmac.2003.11.004

Abstract

A SAR study has been performed in order to evaluate how much the ester function could be a determinant for the anti-human immunodeficiency virus type-1 activity of pyrryl aryl sulfones (PASs), a potent family of non-nucleoside reverse transcriptase (RT) inhibitors discovered in the last years. Twenty-three new esters were prepared with the aim to enhance the inhibitory potency of 4a and 4c, two PAS agents endowed with good activity (EC50 = 0.14 microM) and deprived of cytotoxicity up to >200 microM. None of test derivatives was as potent as 4a and 4c and lacked of selectivity due to their higher cytotoxicity (compounds 22-25). Antiviral activity correlate with an ester ramified chain.

摘要

为了评估酯官能团对吡咯芳基砜（PASs）抗人免疫缺陷病毒1型活性的影响程度，开展了一项构效关系（SAR）研究。PASs是近年来发现的一类有效的非核苷逆转录酶（RT）抑制剂。制备了23种新的酯，目的是提高4a和4c的抑制效力，这两种PAS药物具有良好的活性（EC50 = 0.14 microM），且在高达>200 microM时无细胞毒性。测试的衍生物均不如4a和4c有效，并且由于细胞毒性较高（化合物22 - 25）而缺乏选择性。抗病毒活性与酯的支链有关。

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