鉴定和评估 4-苯胺喹啉（氮杂）类化合物作为抗登革热病毒（DENV）和委内瑞拉马脑炎病毒（VEEV）的有效抑制剂。
Identification and evaluation of 4-anilinoquin(az)olines as potent inhibitors of both dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV).
机构信息
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Bioorg Med Chem Lett. 2021 Nov 15;52:128407. doi: 10.1016/j.bmcl.2021.128407. Epub 2021 Oct 5.
There is an urgent need for novel strategies for the treatment of emerging arthropod-borne viral infections, including those caused by dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV). We prepared and screened focused libraries of 4-anilinoquinolines and 4-anilinoquinazolines for antiviral activity and identified three potent compounds. N-(2,5-dimethoxyphenyl)-6-(trifluoromethyl)quinolin-4-amine (10) inhibited DENV infection with an EC = 0.25 µM, N-(3,4-dichlorophenyl)-6-(trifluoromethyl)quinolin-4-amine (27) inhibited VEEV with an EC = 0.50 µM, while N-(3-ethynyl-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine (54) inhibited VEEV with an EC = 0.60 µM. These series of compounds demonstrated nearly no toxicity with CC values greater than 10 µM in all cases. These promising results provide a future prospective to develop a clinical compound against these emerging viral threats.
目前迫切需要新的策略来治疗新兴的节肢动物传播的病毒感染，包括登革热病毒（DENV）和委内瑞拉马脑炎病毒（VEEV）引起的感染。我们制备并筛选了 4-苯胺喹啉和 4-苯胺喹唑啉的聚焦文库，以评估其抗病毒活性，发现了三种有效的化合物。N-(2,5-二甲氧基苯基)-6-(三氟甲基)喹啉-4-胺（10）对 DENV 的抑制活性 EC₅₀为 0.25 µM，N-(3,4-二氯苯基)-6-(三氟甲基)喹啉-4-胺（27）对 VEEV 的抑制活性 EC₅₀为 0.50 µM，而 N-(3-乙炔基-4-氟苯基)-6,7-二甲氧基喹唑啉-4-胺（54）对 VEEV 的抑制活性 EC₅₀为 0.60 µM。在所有情况下，这些化合物的 CC 值均大于 10 µM，几乎没有毒性。这些有前景的结果为开发针对这些新兴病毒威胁的临床化合物提供了未来的前景。
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