ArticleJournal of medicinal chemistry2015
Original 2-(3-Alkoxy-1H-pyrazol-1-yl)azines Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH).
Article in Journal of medicinal chemistry, 2015. 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, 36 citations in OpenAlex.
- Article
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- Identification of Dihydroorotate Dehydrogenase Inhibitors Using the Cell Painting Assay.Chembiochem : a European journal of chemical biology · 2022Article
- On drug discovery against infectious diseases and academic medicinal chemistry contributions.Beilstein journal of organic chemistry · 2022Article
- On Reuben G. Jones synthesis of 2-hydroxypyrazines.Beilstein journal of organic chemistry · 2022Article
- A Bioluminescent 3CLViruses · 2021Article
- Targeting Lipid Peroxidation for Cancer Treatment.Molecules (Basel, Switzerland) · 2020Review
- CoQ10 and Aging.Biology · 2019Review
- Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties.Molecular cancer therapeutics · 2019Article
- A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage.Nature communications · 2018Article
- A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication.Antiviral research · 2018Article
- N,N-disubstituted azines attenuate LPS-mediated neuroinflammation in microglia and neuronal apoptosis via inhibiting MAPK signaling pathways.BMC neuroscience · 2017Article
- Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate dehydrogenase inhibition.Oncotarget · 2017Article
- Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response.Antimicrobial agents and chemotherapy · 2017Article
- Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase.MedChemComm · 2017Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Following our discovery of human dihydroorotate dehydrogenase (DHODH) inhibition by 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as well as 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyridine, we describe here the syntheses and evaluation of an array of azine-bearing analogues. As in our previous report, the structure-activity study of this series of human DHODH inhibitors was based on a phenotypic assay measuring measles virus replication. Among other inhibitors, this round of syntheses and biological evaluation iteration led to the highly active 5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-3-fluoropyridine. Inhibition of DHODH by this compound was confirmed in an array of in vitro assays, including enzymatic tests and cell-based assays for viral replication and cellular growth. This molecule was found to be more active than the known inhibitors of DHODH, brequinar and teriflunomide, thus opening perspectives for its use as a tool or for the design of an original series of immunosuppressive agent. Moreover, because other series of inhibitors of human DHODH have been found to also affect Plasmodium falciparum DHODH, all the compounds were assayed for their effect on P. falciparum growth. However, the modest in vitro inhibition solely observed for two compounds did not correlate with their inhibition of P. falciparum DHODH.
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