ArticleBioorganic & medicinal chemistry letters2016
Dihydropyrimidinones and -thiones with improved activity against human polyomavirus family members.
Article in Bioorganic & medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- Cycloaddition Reactions of Sulfo-Biginelli Derived Thiadiazines.Organic letters · 2026Article
- Precision in stereochemistry: the integral role of catalytic asymmetric Biginelli reaction in crafting enantiomerically pure dihydropyrimidinones.Molecular diversity · 2024Review
- Article
- An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy.International journal of molecular sciences · 2023Review
- Synthesis and cytotoxicity evaluation of novel cyclic/non-cyclicResearch in pharmaceutical sciences · 2020Article
- Neutral analogs of the heat shock protein 70 (Hsp70) inhibitor, JG-98.Bioorganic & medicinal chemistry letters · 2020Article
- Hsp70 Binds to the Androgen Receptor N-terminal Domain and Modulates the Receptor Function in Prostate Cancer Cells.Molecular cancer therapeutics · 2019Article
- Synthesis and evaluation of esterified Hsp70 agonists in cellular models of protein aggregation and folding.Bioorganic & medicinal chemistry · 2019Article
- Article
- A Five-Component Biginelli-Diels-Alder Cascade Reaction.Frontiers in chemistry · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human polyomaviruses are generally latent but can be reactivated in patients whose immune systems are suppressed. Unfortunately, current therapeutics for diseases associated with polyomaviruses are non-specific, have undefined mechanisms of action, or exacerbate the disease. We previously reported on a class of dihydropyrimidinones that specifically target a polyomavirus-encoded protein, T antigen, and/or inhibit a cellular chaperone, Hsp70, that is required for virus replication. To improve the antiviral activity of the existing class of compounds, we performed Biginelli and modified multi-component reactions to obtain new 3,4-dihydropyrimidin-2(1H)-ones and -thiones for biological evaluation. We also compared how substituents at the N-1 versus N-3 position in the pyrimidine affect activity. We discovered that AMT580-043, a N-3 alkylated dihydropyrimidin-2(1H)-thione, inhibits the replication of a disease-causing polyomavirus in cell culture more potently than an existing drug, cidofovir.
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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.