作为HIV-1整合酶多聚化抑制剂的芳基喹啉的合成与评价
Synthesis and Evaluation of Aryl Quinolines as HIV-1 Integrase Multimerization Inhibitors.
作者信息
Jentsch Nicholas G, Hart Alison P, Hume Jared D, Sun Jian, McNeely Kaitlin A, Lama Chiyang, Pigza Julie A, Donahue Matthew G, Kessl Jacques J
机构信息
Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, Mississippi 39406, United States.
出版信息
ACS Med Chem Lett. 2018 Sep 14;9(10):1007-1012. doi: 10.1021/acsmedchemlett.8b00269. eCollection 2018 Oct 11.
Abstract
HIV-1 integrase multimerization inhibitors have recently been established as an effective class of antiretroviral agents due to their potent ability to inhibit viral replication. Specifically, quinoline-based inhibitors have been shown to effectively impair HIV-1 replication, highlighting the importance of these heterocyclic scaffolds. Pursuant of our endeavors to further develop a library of quinoline-based candidates, we have implemented a structure-activity relationship study of trisubstituted 4-arylquinoline scaffolds that examined the integrase multimerization properties of substitution patterns at the 4-position of the quinoline. Compounds consisting of substituted phenyl rings, heteroaromatics, or polycyclic moieties were examined utilizing an integrase aberrant multimerization assay. -Chloro-4-phenylquinoline and 2,3-benzo[][1,4]dioxine showed noteworthy EC values of 0.10 and 0.08 μM, respectively.
摘要
由于具有强大的抑制病毒复制能力，HIV-1整合酶多聚化抑制剂最近已被确立为一类有效的抗逆转录病毒药物。具体而言，基于喹啉的抑制剂已被证明能有效损害HIV-1复制，凸显了这些杂环支架的重要性。为了进一步开发基于喹啉的候选化合物库，我们对三取代4-芳基喹啉支架进行了构效关系研究，考察了喹啉4位取代模式的整合酶多聚化特性。利用整合酶异常多聚化试验对由取代苯环、杂芳族或多环部分组成的化合物进行了研究。-氯-4-苯基喹啉和2,3-苯并[][1,4]二恶英的EC值分别为0.10和0.08μM，值得关注。
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