ArticleBiochemical pharmacology2004
Structural determinants of efficacy at A3 adenosine receptors: modification of the ribose moiety.
Article in Biochemical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- 4'-Thionucleosides as adenosine AMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Subtle Chemical Changes Cross the Boundary between Agonist and Antagonist: New AJournal of medicinal chemistry · 2021Article
- AMedicinal research reviews · 2018Review
- NJournal of medicinal chemistry · 2017Article
- Synthesis and evaluation of N⁶-substituted apioadenosines as potential adenosine A₃ receptor modulators.Bioorganic & medicinal chemistry · 2014Article
- Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.Bioorganic & medicinal chemistry · 2010Article
- Design and synthesis of N(6)-substituted-4'-thioadenosine-5'-uronamides as potent and selective human A(3) adenosine receptor agonists.Bioorganic & medicinal chemistry · 2009Article
- Synthesis of 3'-acetamidoadenosine derivatives as potential A3 adenosine receptor agonists.Nucleosides, nucleotides & nucleic acids · 2008Article
- Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists.Bioorganic & medicinal chemistry letters · 2008Article
- Stereoselective synthesis of 1'-functionalized-4'-thionucleosides.Nucleosides, nucleotides & nucleic acids · 2007Article
- 2-triazole-substituted adenosines: a new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists.Journal of medicinal chemistry · 2006Article
- Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor.Journal of molecular graphics & modelling · 2006Article
- Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5'-ribofuran-uronamide moiety.Bioorganic & medicinal chemistry letters · 2006Article
- Synthesis of novel apio carbocyclic nucleoside analogues as selective a(3) adenosine receptor agonists.The Journal of organic chemistry · 2005Article
- Exploring human adenosine A3 receptor complementarity and activity for adenosine analogues modified in the ribose and purine moiety.Bioorganic & medicinal chemistry · 2005Article
- The receptor mechanism mediating the contractile response to adenosine on lung parenchymal strips from actively sensitised, allergen-challenged Brown Norway rats.Naunyn-Schmiedeberg's archives of pharmacology · 2005Article
- Purine derivatives as ligands for A3 adenosine receptors.Current topics in medicinal chemistry · 2005Review
- Purine receptors: GPCR structure and agonist design.Molecular interventions · 2004Article
- 2-Substituted adenosine derivatives: affinity and efficacy at four subtypes of human adenosine receptors.Biochemical pharmacology · 2004Article
- Design and synthesis of 3'-ureidoadenosine-5'-uronamides: effects of the 3'-ureido group on binding to the A3 adenosine receptor.Bioorganic & medicinal chemistry letters · 2004Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
We have found previously that structural features of adenosine derivatives, particularly at the N6- and 2-positions of adenine, determine the intrinsic efficacy as A3 adenosine receptor (AR) agonists. Here, we have probed this phenomenon with respect to the ribose moiety using a series of ribose-modified adenosine derivatives, examining binding affinity and activation of the human A3 AR expressed in CHO cells. Both 2'- and 3'-hydroxyl groups in the ribose moiety contribute to A3 AR binding and activation, with 2'-OH being more essential. Thus, the 2'-fluoro substitution eliminated both binding and activation, while a 3'-fluoro substitution led to only a partial reduction of potency and efficacy at the A3 AR. A 5'-uronamide group, known to restore full efficacy in other derivatives, failed to fully overcome the diminished efficacy of 3'-fluoro derivatives. The 4'-thio substitution, which generally enhanced A3 AR potency and selectivity, resulted in 5'-CH2OH analogues (10 and 12) which were partial agonists of the A3 AR. Interestingly, the shifting of the N6-(3-iodobenzyl)adenine moiety from the 1'- to 4'-position had a minor influence on A3 AR selectivity, but transformed 15 into a potent antagonist (16) (Ki = 4.3 nM). Compound 16 antagonized human A3 AR agonist-induced inhibition of cyclic AMP with a K(B) value of 3.0 nM. A novel apio analogue (20) of neplanocin A, was a full A3 AR agonist. The affinities of selected, novel analogues at rat ARs were examined, revealing species differences. In summary, critical structural determinants for human A3 AR activation have been identified, which should prove useful for further understanding the mechanism of receptor activation and development of more potent and selective full agonists, partial agonists and antagonists for A3 ARs.
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