ArticleJournal of medicinal chemistry2017
Double-Winged 3-Hydroxypyrimidine-2,4-diones: Potent and Selective Inhibition against HIV-1 RNase H with Significant Antiviral Activity.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains.Antimicrobial agents and chemotherapy · 2021Trial
- 1,4-Dihydroxy-1,8-napthyridinone (DHN) analogs as HIV-1 reverse transcriptase-associated RNase H inhibitors.Bioorganic chemistry · 2026Article
- Discovery of Small-Molecule Orthopoxvirus Resolvase Inhibitors with Antiviral Activity.Journal of medicinal chemistry · 2025Article
- Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds.Journal of medicinal chemistry · 2023Review
- Repurposing N-hydroxy thienopyrimidine-2,4-diones (HtPD) as inhibitors of human cytomegalovirus pUL89 endonuclease: Synthesis and biological characterization.Bioorganic chemistry · 2022Article
- RNase HI Depletion Strongly Potentiates Cell Killing by Rifampicin in Mycobacteria.Antimicrobial agents and chemotherapy · 2022Article
- 8-Hydroxy-1,6-naphthyridine-7-carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease.ChemMedChem · 2022Article
- 4,5-Dihydroxypyrimidine Methyl Carboxylates, Carboxylic Acids, and Carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease.Journal of medicinal chemistry · 2022Article
- Metal binding 6-arylthio-3-hydroxypyrimidine-2,4-diones inhibited human cytomegalovirus by targeting the pUL89 endonuclease of the terminase complex.European journal of medicinal chemistry · 2021Article
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- Retroviral RNase H: Structure, mechanism, and inhibition.The Enzymes · 2021Review
- 1,2,4-Triazolo[1,5-Molecules (Basel, Switzerland) · 2020Article
- Cutting into the Substrate Dominance: Pharmacophore and Structure-Based Approaches toward Inhibiting Human Immunodeficiency Virus Reverse Transcriptase-Associated Ribonuclease H.Accounts of chemical research · 2020Review
- Coumarin: An emerging antiviral agent.Heliyon · 2020Article
- From cycloheptathiophene-3-carboxamide to oxazinone-based derivatives as allosteric HIV-1 ribonuclease H inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide.Journal of medicinal chemistry · 2019Article
- Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors.Chemical biology & drug design · 2019Article
- Pharmacophore-based design of novel 3-hydroxypyrimidine-2,4-dione subtypes as inhibitors of HIV reverse transcriptase-associated RNase H: Tolerance of a nonflexible linker.European journal of medicinal chemistry · 2019Article
- 6-Arylthio-3-hydroxypyrimidine-2,4-diones potently inhibited HIV reverse transcriptase-associated RNase H with antiviral activity.European journal of medicinal chemistry · 2018Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function yet to be exploited as an antiviral target. One of the possible challenges may be that targeting HIV RNase H is confronted with a steep substrate barrier. We have previously reported a 3-hydroxypyrimidine-2,4-dione (HPD) subtype that potently and selectively inhibited RNase H without inhibiting HIV in cell culture. We report herein a critical redesign of the HPD chemotype featuring an additional wing at the C5 position that led to drastically improved RNase H inhibition and significant antiviral activity. Structure-activity relationship (SAR) concerning primarily the length and flexibility of the two wings revealed important structural features that dictate the potency and selectivity of RNase H inhibition as well as the observed antiviral activity. Our current medicinal chemistry data also revealed that the RNase H biochemical inhibition largely correlated the antiviral activity.
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