ArticleJournal of medicinal chemistry2012
Structural sweet spot for A1 adenosine receptor activation by truncated (N)-methanocarba nucleosides: receptor docking and potent anticonvulsant activity.
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 28 papers, 1 of them a synthesis that pooled it.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics.Progress in neuro-psychopharmacology & biological psychiatry · 2015Pooled it
- Therapeutic Potential Target of Adenosine for Epilepsy: Focusing on Its Interaction with the Molecular Epileptogenic Network.Biomolecules · 2026Review
- Selective modulation of epileptic tissue by an adenosine ABritish journal of pharmacology · 2024Article
- Structure activity relationships of 5-HTEuropean journal of medicinal chemistry · 2023Article
- ATP and adenosine-Two players in the control of seizures and epilepsy development.Progress in neurobiology · 2021Review
- Structure activity relationship of novel antiviral nucleosides against Enterovirus A71.Bioorganic & medicinal chemistry letters · 2020Article
- Design and in Vivo Characterization of AJournal of medicinal chemistry · 2019Article
- Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development.Frontiers in cellular neuroscience · 2019Review
- Probing structure-activity relationship in β-arrestin2 recruitment of diversely substituted adenosine derivatives.Biochemical pharmacology · 2018Article
- Article
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Validation of a Preclinical Drug Screening Platform for Pharmacoresistant Epilepsy.Neurochemical research · 2017Article
- Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge of hippocampal neurons from epileptic rats.Oncotarget · 2017Article
- Hypothermia in mouse is caused by adenosine ANeuropharmacology · 2017Article
- Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HTJournal of medicinal chemistry · 2016Article
- South (S)- and North (N)-Methanocarba-7-Deazaadenosine Analogues as Inhibitors of Human Adenosine Kinase.Journal of medicinal chemistry · 2016Article
- Medicinal chemistry of adenosine, P2Y and P2X receptors.Neuropharmacology · 2016Review
- Rigid Adenine Nucleoside Derivatives as Novel Modulators of the Human Sodium Symporters for Dopamine and Norepinephrine.The Journal of pharmacology and experimental therapeutics · 2016Article
- Article
- John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors.Computational and structural biotechnology journal · 2015Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
A(1) adenosine receptor (AR) agonists display antiischemic and antiepileptic neuroprotective activity, but peripheral cardiovascular side effects impeded their development. SAR study of N(6)-cycloalkylmethyl 4'-truncated (N)-methanocarba-adenosines identified 10 (MRS5474, N(6)-dicyclopropylmethyl, K(i) = 47.9 nM) as a moderately A(1)AR-selective full agonist. Two stereochemically defined N(6)-methynyl group substituents displayed narrow SAR; groups larger than cyclobutyl greatly reduced AR affinity, and those larger or smaller than cyclopropyl reduced A(1)AR selectivity. Nucleoside docking to A(1)AR homology model characterized distinct hydrophobic cyclopropyl subpockets, the larger "A" forming contacts with Thr270 (7.35), Tyr271 (7.36), Ile274 (7.39), and carbon chains of glutamates (EL2) and the smaller subpocket "B" forming contacts between TM6 and TM7. 10 suppressed minimal clonic seizures (6 Hz mouse model) without typical rotarod impairment of A(1)AR agonists. Truncated nucleosides, an appealing preclinical approach, have more druglike physicochemical properties than other A(1)AR agonists. Thus, we identified highly restricted regions for substitution around N(6) suitable for an A(1)AR agonist with anticonvulsant activity.
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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.