ACS Medicinal Chemistry Letters · 2018 · 31 citations · 30 references
Life SciencesChemistryMedicinal ChemistryDrug DiscoveryMolecular VirologyVirologyAntiretroviral TherapyAntiviral AgentsAntiviral PharmacologyEnzyme InhibitionHeterocyclic ChemistryLigand BindingAntiretroviral Drug ClassesAntiviral Structure-activity RelationshipsIntegrase ProteinsIntegron IntegrasePolycyclic HeterocyclesQuinoline ChemistryQuinoline SynthesisViral Replication Control
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 in vitro assay. para-Chloro-4-phenylquinoline 11b and 2,3-benzo[b][1,4]dioxine 15f showed noteworthy EC50 values of 0.10 and 0.08 μM, respectively.
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A role for LEDGF/p75 in targeting HIV DNA integration
Angela Ciuffi, Manuel Llano, Eric M. Poeschla et al. · Nature Medicine · 2005 · 663 citations