ArticleAntimicrobial agents and chemotherapy2010
Structure-activity analysis of vinylogous urea inhibitors of human immunodeficiency virus-encoded ribonuclease H.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Rational Design, Synthesis, and Biological Evaluation of Novel Thiazole/Thiazolidinones Multitarget Anti-Human Immunodeficiency Virus Molecules.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Dihydroxyphenyl- and Heteroaromatic-Based Thienopyrimidinones to Tackle HIV-1 LEDGF/p75-Dependent IN Activity.Molecules (Basel, Switzerland) · 2023Article
- Large Multidomain Protein NMR: HIV-1 Reverse Transcriptase Precursor in Solution.International journal of molecular sciences · 2020Review
- 2-(Arylamino)-6-(trifluoromethyl)nicotinic Acid Derivatives: New HIV-1 RT Dual Inhibitors Active on Viral Replication.Molecules (Basel, Switzerland) · 2020Article
- 1,2,4-Triazolo[1,5-Molecules (Basel, Switzerland) · 2020Article
- From cycloheptathiophene-3-carboxamide to oxazinone-based derivatives as allosteric HIV-1 ribonuclease H inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.ACS infectious diseases · 2019Article
- Article
- A 2-Hydroxyisoquinoline-1,3-Dione Active-Site RNase H Inhibitor Binds in Multiple Modes to HIV-1 Reverse Transcriptase.Antimicrobial agents and chemotherapy · 2017Article
- Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to Genomic Instability.Viruses · 2016Review
- Studies on Cycloheptathiophene-3-carboxamide Derivatives as Allosteric HIV-1 Ribonuclease H Inhibitors.ChemMedChem · 2016Article
- N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand Transfer Inhibitors and Their Activity against RNase H Function of Reverse Transcriptase.Journal of medicinal chemistry · 2015Article
- Structure-activity relationship of pyrrolyl diketo acid derivatives as dual inhibitors of HIV-1 integrase and reverse transcriptase ribonuclease H domain.Journal of medicinal chemistry · 2015Article
- Abasic phosphorothioate oligomers inhibit HIV-1 reverse transcription and block virus transmission across polarized ectocervical organ cultures.Antimicrobial agents and chemotherapy · 2014Article
- Identification of highly conserved residues involved in inhibition of HIV-1 RNase H function by Diketo acid derivatives.Antimicrobial agents and chemotherapy · 2014Article
- The biology and synthesis of α-hydroxytropolones.MedChemComm · 2014Article
- Inhibition of foamy virus reverse transcriptase by human immunodeficiency virus type 1 RNase H inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- Inhibition of the ribonuclease H activity of HIV-1 reverse transcriptase by GSK5750 correlates with slow enzyme-inhibitor dissociation.The Journal of biological chemistry · 2014Article
- Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and their activity against RNase H function of reverse transcriptase.Journal of medicinal chemistry · 2014Article
- Exploiting drug-resistant enzymes as tools to identify thienopyrimidinone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide and N-[3-(aminocarbonyl)-4,5-dimethyl-2-thienyl]-2-furancarboxamide (compounds 1 and 2, respectively) were recently identified to be modestly potent inhibitors of the RNase H activity of HIV-1 and HIV-2 reverse transcriptase (RT). Both compounds shared a 3-CONH(2)-substituted thiophene ring but were otherwise structurally unrelated, which prevented a precise definition of the pharmacophore. We have therefore examined a larger series of vinylogous ureas carrying amide, amine, and cycloalkane modifications of the thiophene ring of compound 1. While cycloheptane- and cyclohexane-substituted derivatives retained potency, cyclopentane and cyclooctane substitutions eliminated activity. In the presence of a cycloheptane ring, modifying the 2-NH(2) or 3-CONH(2) functions decreased the potency. With respect to compound 2, vinylogous ureas whose dimethylthiophene ring contained modifications of the 2-NH(2) and 3-CONH(2) functions were investigated. 2-NH(2)-modified analogs displayed potency equivalent to or enhanced over that of compound 2, the most active of which, compound 16, reflected intramolecular cyclization of the 2-NH(2) and 3-CONH(2) groups. Molecular modeling was used to define an inhibitor binding site in the p51 thumb subdomain, suggesting that an interaction with the catalytically conserved His539 of the p66 RNase H domain could underlie inhibition of RNase H activity. Collectively, our data indicate that multiple functional groups of vinylogous ureas contribute to their potencies as RNase H inhibitors. Finally, single-molecule spectroscopy indicates that vinylogous ureas have the property of altering the reverse transcriptase orientation on a model RNA-DNA hybrid mimicking initiation plus-strand DNA synthesis.
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