ArticleJournal of medicinal chemistry2014
4-amino-1-hydroxy-2-oxo-1,8-naphthyridine-containing compounds having high potency against raltegravir-resistant integrase mutants of HIV-1.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Synthesis of novel biologically active pyridonaphthyridine derivatives by employing FeRSC advances · 2025Article
- Pi-pi stacking interactions with viral DNA contribute to the potency of naphthyridine-based HIV-1 integrase inhibitors.NAR molecular medicine · 2025Article
- Green synthesis and cytotoxic activity of functionalized naphthyridine.Molecular diversity · 2025Article
- Article
- Elucidating the molecular determinants for binding modes of a third-generation HIV-1 integrase strand transfer inhibitor: Importance of side chain and solvent reorganization.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms of HIV-1 integrase resistance to dolutegravir and potent inhibition of drug-resistant variants.Science advances · 2023Article
- INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay.Viruses · 2021Article
- Naphthyridine Derivatives Induce Programmed Cell Death inPharmaceuticals (Basel, Switzerland) · 2021Article
- Gram-Scale Synthesis of 1,8-Naphthyridines in Water: The Friedlander Reaction Revisited.ACS omega · 2021Article
- HIV-1 Integrase Inhibitors with Modifications That Affect Their Potencies against Drug Resistant Integrase Mutants.ACS infectious diseases · 2021Article
- Review
- Retroviral integrase: Structure, mechanism, and inhibition.The Enzymes · 2021Article
- Structural Biology of HIV Integrase Strand Transfer Inhibitors.Trends in pharmacological sciences · 2020Review
- Structural basis for strand-transfer inhibitor binding to HIV intasomes.Science (New York, N.Y.) · 2020Article
- Developing and Evaluating Inhibitors against the RNase H Active Site of HIV-1 Reverse Transcriptase.Journal of virology · 2018Article
- Efficacies of Cabotegravir and Bictegravir against drug-resistant HIV-1 integrase mutants.Retrovirology · 2018Article
- Structure-Guided Optimization of HIV Integrase Strand Transfer Inhibitors.Journal of medicinal chemistry · 2017Article
- Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives.Molecules (Basel, Switzerland) · 2016Article
- Selectivity for strand-transfer over 3'-processing and susceptibility to clinical resistance of HIV-1 integrase inhibitors are driven by key enzyme-DNA interactions in the active site.Nucleic acids research · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
There are currently three HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) approved by the FDA for the treatment of AIDS. However, the emergence of drug-resistant mutants emphasizes the need to develop additional agents that have improved efficacies against the existent resistant mutants. As reported herein, we modified our recently disclosed 1-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamides IN inhibitors to develop compounds that have improved efficacies against recombinant IN in biochemical assays. These new compounds show single-digit nanomolar antiviral potencies against HIV vectors that carry wild-type (WT) IN in a single round replication assay and have improved potency against vectors harboring the major forms of drug resistant IN mutants. These compounds also have low toxicity for cultured cells, which in several cases, results in selectivity indices (CC50/EC50) of greater than 10000. The compounds have the potential, with additional structural modifications, to yield clinical agents that are effective against the known strains of resistant viruses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.