ArticleJournal of medicinal chemistry2012
Non-nucleoside inhibitors of the measles virus RNA-dependent RNA polymerase: synthesis, structure-activity relationships, and pharmacokinetics.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed.
- Structural insights into measles virus RNA synthesis regulation and pan-paramyxoviral polymerase inhibition by ERDRP-0519.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Protection against lethal canine distemper virus infection by a dual epitope-targeting synthetic antibody.Nature communications · 2026Article
- Structural basis of measles virus polymerase inhibition by nonnucleoside inhibitor ERDRP-0519.Nature communications · 2025Article
- Structural basis of paramyxo- and pneumovirus polymerase inhibition by non-nucleoside small-molecule antivirals.Antimicrobial agents and chemotherapy · 2024Review
- Review
- Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors.iScience · 2024Article
- Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds.Viruses · 2022Review
- Article
- Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding.Nature communications · 2021Article
- Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses.RSC medicinal chemistry · 2021Review
- Therapeutic targeting of measles virus polymerase with ERDRP-0519 suppresses all RNA synthesis activity.PLoS pathogens · 2021Article
- Advances in Antiviral Therapy for Subacute Sclerosing Panencephalitis.Molecules (Basel, Switzerland) · 2021Review
- Anno 2021: Which antivirals for the coming decade?Annual reports in medicinal chemistry · 2021Article
- Synthesis, Crystal Structures and Anticancer Studies of Morpholinyldithiocarbamato Cu(II) and Zn(II) Complexes.Molecules (Basel, Switzerland) · 2020Article
- Measles Resurgence and Drug Development.Current opinion in virology · 2020Review
- Measles Encephalitis: Towards New Therapeutics.Viruses · 2019Review
- Development of an allosteric inhibitor class blocking RNA elongation by the respiratory syncytial virus polymerase complex.The Journal of biological chemistry · 2018Article
- Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review.Molecules (Basel, Switzerland) · 2018Review
- Organization, Function, and Therapeutic Targeting of the Morbillivirus RNA-Dependent RNA Polymerase Complex.Viruses · 2016Review
- A pioneering countermeasure against measles virus.Annals of translational medicine · 2015Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The measles virus (MeV), a member of the paramyxovirus family, is an important cause of pediatric morbidity and mortality worldwide. In an effort to provide therapeutic treatments for improved measles management, we previously identified a small, non-nucleoside organic inhibitor of the viral RNA-dependent RNA polymerase by means of high-throughput screening. Subsequent structure-activity relationship (SAR) studies around the corresponding pyrazole carboxamide scaffold led to the discovery of 2 (AS-136a), a first generation lead with low nanomolar potency against life MeV and attractive physical properties suitable for development. However, its poor water solubility and low oral bioavailability (F) in rat suggested that the lead could benefit from further SAR studies to improve the biophysical characteristics of the compound. Optimization of in vitro potency and aqueous solubility led to the discovery of 2o (ERDRP-00519), a potent inhibitor of MeV (EC(50) = 60 nM) with an aqueous solubility of approximately 60 μg/mL. The agent shows a 10-fold exposure (AUC/C(max)) increase in the rat model relative to 2, displays near dose proportionality in the range of 10-50 mg/kg, and exhibits good oral bioavailability (F = 39%). The significant solubility increase appears linked to the improved oral bioavailability.
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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.