Imidazolidinones and Imidazolidine‐2,4‐diones as Antiviral Agents

Abstract

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.

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

“…Hence, to overcome such situation presently, available more resources, much faster, and advance scientific techniques need to be adopted and explored. Earlier, a number of studies have proposed various traditional and specific methods for the identification of different chemical entities and demonstrated their selective inhibition mechanism and inhibitory efficacy against NS3‐NS2B protease complex at different levels …”

New 2‐Oxoimidazolidine Derivatives: Design, Synthesis and Evaluation of Anti‐BK Virus Activities in Vitro

“…Therefore, these and possibly other proteins of the viral cycle can be targets for medication. Analogous proteins of other viruses have been shown to be targets for 2‐oxoimidazolidine derivatives, including some proteases of HCV and dengue virus, and capsid protein VP1 of human enterovirus 71 . Although the mechanism of action of the synthesized imidazolidine compounds reported here is still unknown, these proteins may be taken as likely targets.…”

“…Analogous proteins of other viruses have been shown to be targets for 2-oxoimidazolidine derivatives, including some proteases of HCV and dengue virus, and capsid protein VP1 of human enterovirus 71. [28] Although the mechanism of action of the synthesized imidazolidine compounds reported here is still unknown, these proteins may be taken as likely targets. New ideas are required for an in-depth study of the BKPyV life cycle, which will also help identify additional mechanisms that could become targets for the development of effective antiviral drugs.…”

Antivirals against human polyomaviruses: Leaving no stone unturned

“…2-Oxoimidazolidines inhibit virus replication such as dengue, enterovirus, HCV and HIV. 374 A group of 2-oxoimidazolidine derivatives was evaluated against BKPyV (Gardner-strain) in HFF cells. 238 The calculated EC 50 , EC 90 and CC 50 of compound-5 was 5.43, 145.56 and 150 µM, and an SI 50 of 28 (Table 4).…”