ArticleChemical biology & drug design2012
Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors.
Article in Chemical biology & drug design, 2012. 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, 28 citations in OpenAlex.
- On the Question of the Full Selective Synthesis of Potentially Bioactive of 2-(Molecules (Basel, Switzerland) · 2026Article
- 2-(Trihydroxyphenyl)thienopyrimidinones as Key Scaffolds for Targeting a Novel Allosteric Site of HIV-1 Integrase.Molecules (Basel, Switzerland) · 2025Article
- Recent Developments in the Synthesis of HIV-1 Integrase Strand Transfer Inhibitors Incorporating Pyridine Moiety.International journal of molecular sciences · 2023Review
- New Aspects of the Reaction of Thioacetamide and N-Substituted Maleimides.Molecules (Basel, Switzerland) · 2022Article
- Structural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures.Nature communications · 2021Article
- An Overview of the Biological Activity of Pyrrolo[3,4-Pharmaceuticals (Basel, Switzerland) · 2021Review
- Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA ofMolecules (Basel, Switzerland) · 2020Article
- Structure-Guided Optimization of HIV Integrase Strand Transfer Inhibitors.Journal of medicinal chemistry · 2017Article
- Drug resistant integrase mutants cause aberrant HIV integrations.Retrovirology · 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
- HIV-1 Integrase Strand Transfer Inhibitors with Reduced Susceptibility to Drug Resistant Mutant Integrases.ACS chemical biology · 2016Article
- 6,7-Dihydroxyisoindolin-1-one and 7,8-Dihydroxy-3,4-Dihydroisoquinolin- 1(2H)-one Based HIV-1 Integrase Inhibitors.Current topics in medicinal chemistry · 2016Review
- 4-amino-1-hydroxy-2-oxo-1,8-naphthyridine-containing compounds having high potency against raltegravir-resistant integrase mutants of HIV-1.Journal of medicinal chemistry · 2014Article
- Bicyclic 1-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-containing HIV-1 integrase inhibitors having high antiviral potency against cells harboring raltegravir-resistant integrase mutants.Journal of medicinal chemistry · 2014Article
- 6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 integrase inhibitors.Bioorganic & medicinal chemistry letters · 2012Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
HIV-1 integrase (IN) is a validated therapeutic target for the treatment of AIDS. However, the emergence of resistance to raltegravir, the sole marketed FDA-approved IN inhibitor, emphasizes the need to develop second-generation inhibitors that retain efficacy against clinically relevant IN mutants. We report herein bicyclic hydroxy-1H-pyrrolopyridine-triones as a new family of HIV-1 integrase inhibitors that were efficiently prepared using a key 'Pummerer cyclization deprotonation cycloaddition' cascade of imidosulfoxides. In in vitro HIV-1 integrase assays, the analogs showed low micromolar inhibitory potencies with selectivity for strand transfer reactions as compared with 3'-processing inhibition. A representative inhibitor (5e) retained most of its inhibitory potency against the three major raltegravir-resistant IN mutant enzymes, G140S/Q148H, Y143R, and N155H. In antiviral assays employing viral vectors coding these IN mutants, compound 5e was approximately 200- and 20-fold less affected than raltegravir against the G140S/Q148H and Y143R mutations, respectively. Against the N155H mutation, 5e was approximately 10-fold less affected than raltegravir. Thus, our new compounds represent a novel structural class that may be further developed to overcome resistance to raltegravir, particularly in the case of the G140S/Q148H mutations.
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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.