ArticleEuropean journal of medicinal chemistry2017
Synthesis and pre-clinical studies of new amino-acid ester thiazolide prodrugs.
Article in European journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- From hydroxychloroquine to ivermectin: what are the anti-viral properties of anti-parasitic drugs to combat SARS-CoV-2?Journal of travel medicine · 2021Pooled it
- Enhancing thiazolide efficacy: C-4 aryl modifications drive selective SARS-CoV-2 inhibition.Future medicinal chemistry · 2025Article
- Convenient syntheses of 2-acylamino-4-halothiazoles and acylated derivatives using a versatile Boc-intermediate.RSC advances · 2024Article
- Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity.ACS bio & med chem Au · 2023Article
- Therapeutic potential of salicylamide derivatives for combating viral infections.Medicinal research reviews · 2023Review
- Systemic efficacy onParasitology · 2021Article
- Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors.ACS medicinal chemistry letters · 2021Article
- Viral burden, inflammatory milieu and CD8Influenza and other respiratory viruses · 2020Article
- Medicinal chemistry strategies toward host targeting antiviral agents.Medicinal research reviews · 2020Review
- Thiazolides promote G1 cell cycle arrest in colorectal cancer cells by targeting the mitochondrial respiratory chain.Oncogene · 2020Article
- Amixicile: A Concept Therapeutic for Treatment of Chronic Anaerobic Infections.British journal of gastroenterology · 2020Article
- Cytoplasmic RNA Sensor Pathways and Nitazoxanide Broadly Inhibit Intracellular Mycobacterium tuberculosis Growth.iScience · 2019Article
- Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference.Antiviral research · 2019Review
- Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference.Antiviral research · 2018Article
- Influenza antivirals currently in late-phase clinical trial.Influenza and other respiratory viruses · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thiazolides are polypharmacology agents with at least three mechanisms of action against a broad spectrum of parasites, bacteria and viruses. In respiratory viruses they inhibit the replication of orthomyxoviridae and paramyxoviridae at a post-translational level. Nitazoxanide 1a, the prototype thiazolide, was originally developed as an antiparasitic agent and later repurposed for the treatment of viral respiratory infections. The second generation thiazolides following nitazoxanide, such as the 5-chloro analogue RM-5038 2a, are also broad-spectrum antiviral agents as we have reported. Both 1a and its effective circulating metabolite, tizoxanide 1b, are 5-nitrothiazole derivatives, while RM-5038 2a and its de-acetyl derivative RM-4848 2b are the corresponding 5-chloro derivatives. Recently 1a has completed phase II-III clinical trials in the United States, Canada, Australia and New Zealand in a total of 2865 adults and adolescents of at least 12 months of age with viral acute respiratory illness. Since its biodisposition is primarily seen in the gastro-intestinal tract, its efficacy in systemic viral diseases requires relatively high oral doses. The chemical synthesis of new derivatives with a better systemic absorption was therefore urgently needed. In order to improve their systemic absorption, new amino-ester prodrug derivatives of 1b and RM4848 2b were prepared and tested for their animal pharmacology, pharmacokinetics and toxicology. RM-5061 8a in rats showed 7-fold higher blood concentration compared to 1a: absolute bioavailability increased from 3 to 20%, with a good safety profile in animal safety pharmacology and toxicology.
Indexed as
Identifiers
What OpenQuestion holds
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.