ArticleEuropean journal of medicinal chemistry2019
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.
Article in European journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- 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
- Identification of HIV-1 Reverse Transcriptase-Associated Ribonuclease H Inhibitors Based on 2-Hydroxy-1,4-naphthoquinone Mannich Bases.Molecules (Basel, Switzerland) · 2025Article
- Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities.RSC advances · 2023Article
- Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds.Journal of medicinal chemistry · 2023Review
- Targeting Metalloenzymes: The "Achilles' Heel" of Viruses and Parasites.Pharmaceuticals (Basel, Switzerland) · 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
- Quinolinonyl Non-Diketo Acid Derivatives as Inhibitors of HIV-1 Ribonuclease H and Polymerase Functions of Reverse Transcriptase.Journal of medicinal chemistry · 2021Article
- Retroviral RNase H: Structure, mechanism, and inhibition.The Enzymes · 2021Review
- Pyrrolyl Pyrazoles as Non-Diketo Acid Inhibitors of the HIV-1 Ribonuclease H Function of Reverse Transcriptase.ACS medicinal chemistry letters · 2020Article
- Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root.European journal of medicinal chemistry · 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
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10 authors.
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Abstract
The pharmacophore of active site inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated RNase H typically entails a flexible linker connecting the chelating core and the hydrophobic aromatics. We report herein that novel 3-hydroxypyrimidine-2,4-dione (HPD) subtypes with a nonflexible C-6 carbonyl linkage exhibited potent and selective biochemical inhibitory profiles with strong RNase H inhibition at low nM, weak to moderate integrase strand transfer (INST) inhibition at low μM, and no to marginal RT polymerase (pol) inhibition up to 10 μM. A few analogues also demonstrated significant antiviral activity without cytotoxicity. The overall inhibitory profile is comparable to or better than that of previous HPD subtypes with a flexible C-6 linker, suggesting that the nonflexible carbonyl linker can be tolerated in the design of novel HIV RNase H active site inhibitors.
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