ArticleMolecular pharmacology2002
Selective allosteric enhancement of agonist binding and function at human A3 adenosine receptors by a series of imidazoquinoline derivatives.
Article in Molecular pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- From empirical screening to lipid trolling: the evolution of extrahelical allosteric modulators of AMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Bitopic AJournal of medicinal chemistry · 2025Article
- Lipid Trolling to Optimize AJournal of medicinal chemistry · 2024Article
- Extrahelical Binding Site for a 1Molecular pharmacology · 2024Article
- Structure-Activity Studies of 1Journal of medicinal chemistry · 2022Article
- Characterization of Dual-Acting AACS pharmacology & translational science · 2022Article
- Allosteric Modulation of Adenosine AInternational journal of molecular sciences · 2022Review
- Update on the recent development of allosteric modulators for adenosine receptors and their therapeutic applications.Frontiers in pharmacology · 2022Review
- AMedicinal research reviews · 2018Review
- Species differences and mechanism of action of APurinergic signalling · 2018Article
- Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.Journal of computational chemistry · 2017Article
- Allosteric interactions at adenosine A(1) and A(3) receptors: new insights into the role of small molecules and receptor dimerization.British journal of pharmacology · 2014Review
- Protection from myocardial ischemia/reperfusion injury by a positive allosteric modulator of the A₃ adenosine receptor.The Journal of pharmacology and experimental therapeutics · 2012Article
- Functionally biased modulation of A(3) adenosine receptor agonist efficacy and potency by imidazoquinolinamine allosteric enhancers.Biochemical pharmacology · 2011Article
- International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update.Pharmacological reviews · 2011Review
- Comparative analysis of species-specific ligand recognition in Toll-like receptor 8 signaling: a hypothesis.PloS one · 2011Article
- Allosteric modulation of purine and pyrimidine receptors.Advances in pharmacology (San Diego, Calif.) · 2011Review
- Novel 2- and 4-substituted 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the A3 adenosine receptor.Journal of medicinal chemistry · 2009Article
- Allosteric modulation of adenosine receptors.Purinergic signalling · 2009Article
- Flexible modulation of agonist efficacy at the human A3 adenosine receptor by the imidazoquinoline allosteric enhancer LUF6000.BMC pharmacology · 2008Article
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6 authors.
Funding
Abstract
We have identified a series of 1H-imidazo-[4,5-c]quinolines as selective allosteric enhancers of human A3 adenosine receptors. Several of these compounds potentiated both the potency and maximal efficacy of agonist-induced responses and selectively decreased the dissociation of the agonist N6-(4-amino-3-[125I]iodobenzyl)-5'-N-methylcarboxamidoadenosine from human A3 adenosine receptors. There was no effect on the dissociation of the antagonist [3H]8-ethyl-4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2.1-i]purin-5-one (PSB-11) from the A3 receptors, as well as [3H]N6-[(R)-phenylisopropyl]adenosine from rat brain A1 receptors and [3H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5'-N-ethylcarboxamidoadenosine from rat striatal A2A receptors, suggesting the selective enhancement of agonist binding at A3 receptors. The analogs were tested as antagonists of competitive binding at human A3 receptors, and K(i) values ranging from 120 nM to 101 microM were observed; as for many allosteric modulators of G protein-coupled receptors, an orthosteric effect was also present. The most promising leads from the present set of analogs seem to be the 2-cyclopentyl-1H-imidazo[4,5-c]quinoline derivatives, of which the 4-phenylamino analog DU124183 had the most favorable degree of allosteric modulation versus receptor antagonism. The inhibition of forskolin-stimulated cyclic AMP accumulation in intact cells that express human A3 receptors was employed as a functional index of A3 receptor activation. The enhancer DU124183 caused a marked leftward shift of the concentration-response curve of the A3 receptor agonists in the presence of antagonist and, surprisingly, a potentiation of the maximum agonist efficacy by approximately 30%. Thus, we have identified a novel structural lead for developing allosteric enhancers of A3 adenosine receptors; such enhancers may be useful for treating brain ischemia and other hypoxic conditions.
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