ArticleBiochemical pharmacology2003
N6-Substituted adenosine derivatives: selectivity, efficacy, and species differences at A3 adenosine receptors.
Article in Biochemical pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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
85 citing papers in PubMed, 134 citations in OpenAlex.
- Chiral-Modified Nucleoside Analogues: From Bioactivity to Therapeutic Applications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Therapeutic potential of adenosine receptor modulators in cancer treatment.RSC advances · 2025Review
- Structure-Activity Relationship of Truncated 4'-Selenonucleosides: AACS medicinal chemistry letters · 2024Article
- Verification of In Vitro Anticancer Activity and Bioactive Compounds in Cordyceps Militaris-Infused Sweet Potato Shochu Spirits.Molecules (Basel, Switzerland) · 2024Article
- Species dependence of APurinergic signalling · 2023Review
- Expression and Impact of Adenosine AInternational journal of molecular sciences · 2023Article
- AInternational review of neurobiology · 2023Article
- Adamantane-Substituted Purine Nucleosides: Synthesis, Host-Guest Complexes with β-Cyclodextrin and Biological Activity.International journal of molecular sciences · 2022Article
- Design, Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives Targeting hAMolecules (Basel, Switzerland) · 2022Article
- Exploration of chalcones and related heterocycle compounds as ligands of adenosine receptors: therapeutics development.Molecular diversity · 2022Review
- Selective AACS medicinal chemistry letters · 2022Article
- APharmaceuticals (Basel, Switzerland) · 2022Article
- Pharmacological characterization of DPTN and other selective APurinergic signalling · 2021Article
- Subtle Chemical Changes Cross the Boundary between Agonist and Antagonist: New AJournal of medicinal chemistry · 2021Article
- The role of peripheral adenosine receptors in glutamate-induced pain nociceptive behavior.Purinergic signalling · 2021Article
- Adenosine receptors as promising targets for the management of ocular diseases.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Review
- Nucleotide P2YPurinergic signalling · 2020Article
- Direct Comparison of (N)-Methanocarba and Ribose-Containing 2-Arylalkynyladenosine Derivatives as AACS medicinal chemistry letters · 2020Article
- Assessment of biased agonism at the ABiochemical pharmacology · 2020Article
- Truncated (N)-Methanocarba Nucleosides as Partial Agonists at Mouse and Human AJournal of medicinal chemistry · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The activation of the human A(3) adenosine receptor (AR) by a wide range of N(6)-substituted adenosine derivatives was studied in intact CHO cells stably expressing this receptor. Selectivity of binding at rat and human ARs was also determined. Among N(6)-alkyl substitutions, small N(6)-alkyl groups were associated with selectivity for human A(3)ARs vs. rat A(3)ARs, and multiple points of branching were associated with decreased hA(3)AR efficacy. N(6)-Cycloalkyl-substituted adenosines were full (</=5 carbons) or partial (>/=6 carbons) hA(3)AR agonists. N(6)-(endo-Norbornyl)adenosine 13 was the most selective for both rat and human A(1)ARs. Numerous N(6)-arylmethyl analogues, including substituted benzyl, tended to be more potent in binding to A(1) and A(3) vs. A(2A)ARs (with variable degrees of partial to full A(3)AR agonisms). A chloro substituent decreased the efficacy depending on its position on the benzyl ring. The A(3)AR affinity and efficacy of N(6)-arylethyl adenosines depended highly on stereochemistry, steric bulk, and ring constraints. Stereoselectivity of binding was demonstrated for N(6)-(R-1-phenylethyl)adenosine vs. N(6)-(S-1-phenylethyl)adenosine, as well as for the N(6)-(1-phenyl-2-pentyl)adenosine, at the rat, but not human A(3)AR. Interestingly, DPMA, a potent agonist for the A(2A)AR (K(i)=4nM), was demonstrated to be a moderately potent antagonist for the human A(3)AR (K(i)=106nM). N(6)-[(1S,2R)-2-Phenyl-1-cyclopropyl]adenosine 48 was 1100-fold more potent in binding to human (K(i)=0.63nM) than rat A(3)ARs. Dual acting A(1)/A(3) agonists (N(6)-3-chlorobenzyl- 29, N(6)-(S-1-phenylethyl)- 39, and 2-chloro-N(6)-(R-phenylisopropyl)adenosine 53) might be useful for cardioprotection.
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.