ArticleEuropean journal of medicinal chemistry2018
6-Arylthio-3-hydroxypyrimidine-2,4-diones potently inhibited HIV reverse transcriptase-associated RNase H with antiviral activity.
Article in European journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Chemical synthesis, bioinformatics and antiproliferative studies of novel pyrimidin-4-yl-1H-pyrazole derivatives in chronic myeloid cancer cells.Scientific reports · 2026Article
- Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- Structure-Based Design of Novel Thiazolone[3,2-Molecules (Basel, Switzerland) · 2024Article
- Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.ACS chemical biology · 2023Review
- Strategies to overcome HIV drug resistance-current and future perspectives.Frontiers in microbiology · 2023Review
- Repurposing N-hydroxy thienopyrimidine-2,4-diones (HtPD) as inhibitors of human cytomegalovirus pUL89 endonuclease: Synthesis and biological characterization.Bioorganic chemistry · 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
- Retroviral RNase H: Structure, mechanism, and inhibition.The Enzymes · 2021Review
- Targeting HIV-1 RNase H:Viruses · 2020Article
- 2-(Arylamino)-6-(trifluoromethyl)nicotinic Acid Derivatives: New HIV-1 RT Dual Inhibitors Active on Viral Replication.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
- 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
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11 authors at 4 institutions in 1 country.
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Abstract
Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not targeted by current drugs. Although a few chemotypes have been reported to inhibit HIV RNase H in biochemical assays, their general lack of significant antiviral activity in cell culture necessitates continued efforts in identifying highly potent RNase H inhibitors to confer antiviral activity. We report herein the design, synthesis, biochemical and antiviral evaluations of a new 6-arylthio subtype of the 3-hydroxypyrimidine-2,4-dione (HPD) chemotype. In biochemical assays these new analogues inhibited RT RNase H in single-digit nanomolar range without inhibiting RT polymerase (pol) at concentrations up to 10 μM, amounting to exceptional biochemical inhibitory selectivity. Many analogues also inhibited integrase strand transfer (INST) activity in low to sub micromolar range. More importantly, most analogues inhibited HIV in low micromolar range without cytotoxicity. In the end, compound 13j (RNase H IC
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