Department of Process Chemistry, Dr. Reddy's Lab Ltd., CTO-III, IDA, Bollaram, Hyderabad, 502325, India.
ChemMedChem. 2019 Feb 5;14(3):291-302. doi: 10.1002/cmdc.201800686. Epub 2019 Jan 11.
Imidazolidinones and imidazolidine-2,4-diones are important classes of heterocyclic compounds that possess potent activities against several viruses such as dengue virus, enterovirus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV). The first imidazolidinone derivative as an anti-HIV agent was reported in 1996. Imidazolidinones inhibit HIV aspartic protease activity, and also act as CCR5 co-receptor antagonists. Significant effort has been devoted to the design of various imidazolidinone analogues that are active against drug-resistant HIV strains, with fewer side effects. Different scaffolds have been designed through both rational drug design strategies and computer-aided drug design. Imidazolidinones have been found to be potent against HIV, and preclinical studies are currently in progress. There are some reports of imidazolidinones as having both anti-HCV and anti-dengue virus activity, and more research has yet to be done along these lines. These compounds inhibit NS3 serine protease of HCV, and NS2B-NS3 protease of dengue virus. Pyridyl-imidazolidinones possess very specific and potent activity against human enterovirus 71 (EV71) by targeting the EV71 capsid protein VP1, and inhibiting viral adsorption and/or viral RNA uncoating.
咪唑烷酮和咪唑烷-2,4-二酮是一类重要的杂环化合物，对登革热病毒、肠道病毒、丙型肝炎病毒 (HCV) 和人类免疫缺陷病毒 (HIV) 等多种病毒具有很强的活性。1996 年首次报道了作为抗 HIV 药物的第一个咪唑烷酮衍生物。咪唑烷酮通过抑制 HIV 天冬氨酸蛋白酶活性，也作为 CCR5 共受体拮抗剂发挥作用。人们致力于设计各种针对耐药 HIV 株的活性更强、副作用更少的咪唑烷酮类似物。通过合理的药物设计策略和计算机辅助药物设计，设计了不同的支架。咪唑烷酮对 HIV 具有很强的抑制作用，目前正在进行临床前研究。有一些关于咪唑烷酮具有抗 HCV 和抗登革热病毒活性的报道，需要进一步研究。这些化合物通过抑制 HCV 的 NS3 丝氨酸蛋白酶和登革热病毒的 NS2B-NS3 蛋白酶来发挥作用。吡啶基-咪唑烷酮通过靶向 EV71 衣壳蛋白 VP1，抑制病毒吸附和/或病毒 RNA 脱壳，对人肠道病毒 71 (EV71) 具有非常特异和强效的活性。
