ArticlePurinergic signalling2015
Efficient, large-scale synthesis and preclinical studies of MRS5698, a highly selective A3 adenosine receptor agonist that protects against chronic neuropathic pain.
Article in Purinergic signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 51 citations in OpenAlex.
- The long march towards testing the adenosine receptor agonism hypothesis for human cerebroprotection: The story of the APurinergic signalling · 2026Review
- (N)-Methanocarba Adenosine Derivatives as Dual Modulators of P-Glycoprotein and ABCG2 Transporters.Journal of medicinal chemistry · 2026Article
- (N)-Methanocarba-adenosines as monoamine transporter allosteric inhibitors: Extended NEuropean journal of medicinal chemistry · 2026Article
- Review
- Mitochondrial AThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Potent and Selective Human 5-HTJournal of medicinal chemistry · 2024Article
- Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native APurinergic signalling · 2024Article
- 2-Substituted (N)-Methanocarba AACS pharmacology & translational science · 2024Article
- Covalently Binding Adenosine APurinergic signalling · 2024Article
- Structure activity relationships of 5-HTEuropean journal of medicinal chemistry · 2023Article
- First Potent Macrocyclic AACS pharmacology & translational science · 2023Article
- Therapeutic Potential of Highly Selective AMolecules (Basel, Switzerland) · 2022Review
- Interaction of AEuropean journal of medicinal chemistry · 2022Article
- AEuropean journal of medicinal chemistry · 2022Article
- Optical Control of Adenosine AFrontiers in immunology · 2022Article
- Expanding the repertoire of methanocarba nucleosides from purinergic signaling to diverse targets.RSC medicinal chemistry · 2021Review
- Convergent synthesis of 2-thioether-substituted (RSC advances · 2021Article
- Optical control of adenosine APharmacological research · 2021Article
- Uncovering the Mechanisms of Adenosine Receptor-Mediated Pain Control: Focus on the AInternational journal of molecular sciences · 2021Review
- Adenosine Metabotropic Receptors in Chronic Pain Management.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
We reported that 2-(3,4-difluorophenylethynyl)-N (6)-3-chlorobenzyl (N)-methanocarba adenosine derivative 1 (MRS5698) binds selectively to human and mouse A3 adenosine receptors (A3ARs, K i 3 nM). It is becoming an important pharmacological tool for defining A3AR effects and is orally active in a chronic neuropathic pain model. Here, we introduce a new synthetic route for MRS5698 from D-ribose, suitable for a scale-up on a multi-gram scale, and we measure in vitro and in vivo ADME-Tox parameters. MRS5698 was very stable in vitro, failed to inhibit CYPs at <10 μM, and was largely bound to plasma proteins. It was well tolerated in the rat at doses of ≤200 mg/kg i.p. A 1 mg/kg i.p. dose in the mouse displayed t 1/2 of 1.09 h and plasma Cmax of 204 nM at 1 h with an AUC of 213 ng × h/mL. CACO-2 bidirectional transport studies suggested intestinal efflux of MRS5698 (efflux ratio 86). Although the oral %F is only 5 %, the beneficial effect to reverse pain lasted for at least 2 h in the CCI model in rats, using the same vehicle for oral administration of a high dose. The stability, low toxicity, lack of CYP interaction, pharmacokinetic half-life, and in vivo efficacy suggest that MRS5698 is a preferred compound for further consideration as a treatment for neuropathic pain.
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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.