ArticleJournal of medicinal chemistry1998
Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y1 receptors.
Article in Journal of medicinal chemistry, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 133 citations in OpenAlex.
- Advances in nucleotide-based P2Y₁ antagonism: implications for cardiovascular therapeutics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Retrotrapezoid nucleus chemoreception: mechanisms of function and contributions to disordered breathing in disease.Trends in neurosciences · 2025Review
- Neurotransmitters responsible for purinergic motor neurotransmission and regulation of GI motility.Autonomic neuroscience : basic & clinical · 2021Article
- Medicinal chemistry of P2 and adenosine receptors: Common scaffolds adapted for multiple targets.Biochemical pharmacology · 2021Review
- Burnstock and the legacy of the inhibitory junction potential and P2Y1 receptors.Purinergic signalling · 2021Review
- Demystifying P2YJournal of chemical information and modeling · 2017Article
- New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors.European journal of medicinal chemistry · 2016Article
- Purinergic neuromuscular transmission in the gastrointestinal tract; functional basis for future clinical and pharmacological studies.British journal of pharmacology · 2014Review
- Fluorescent techniques for discovery and characterization of phosphopantetheinyl transferase inhibitors.The Journal of antibiotics · 2014Article
- P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure.Hypertension (Dallas, Tex. : 1979) · 2013Article
- P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential.CNS & neurological disorders drug targets · 2012Review
- Effects of P2Y(1) receptor antagonism on the reactivity of platelets from patients with stable coronary artery disease using aspirin and clopidogrel.British journal of pharmacology · 2012Article
- β-nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons.Gastroenterology · 2011Article
- ATP induces synaptic gene expressions in cortical neurons: transduction and transcription control via P2Y1 receptors.Molecular pharmacology · 2010Article
- P2Y nucleotide receptors: promise of therapeutic applications.Drug discovery today · 2010Review
- Frontal affinity chromatography-mass spectrometry useful for characterization of new ligands for GPR17 receptor.Journal of medicinal chemistry · 2010Article
- P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions.Integrative biology : quantitative biosciences from nano to macro · 2010Article
- P2Y(1) receptors mediate inhibitory neuromuscular transmission in the rat colon.British journal of pharmacology · 2009Article
- Characterization of Calcium-Mediated Intracellular and Intercellular Signaling in the rMC-1 Glial Cell Line.Cellular and molecular bioengineering · 2009Article
- ATP and NO dually control migration of microglia to nerve lesions.Developmental neurobiology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Adenosine 3',5'- and 2',5'-bisphosphates previously were demonstrated to act as competitive antagonists at the P2Y1 receptor (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329). 2'- and 3'-Deoxyadenosine bisphosphate analogues containing various structural modifications at the 2- and 6-positions of the adenine ring, on the ribose moiety, and on the phosphate groups have been synthesized with the goal of developing more potent and selective P2Y1 antagonists. Single-step phosphorylation reactions of adenosine nucleoside precursors were carried out. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-MeSATP (antagonist effect). Both 2'- and 3'-deoxy modifications were well tolerated. The N6-methyl modification both enhanced antagonistic potency (IC50 330 nM) of 2'-deoxyadenosine 3',5'-bisphosphate by 17-fold and eliminated residual agonist properties observed with the lead compounds. The N6-ethyl modification provided intermediate potency as an antagonist, while the N6-propyl group completely abolished both agonist and antagonist properties. 2-Methylthio and 2-chloro analogues were partial agonists of intermediate potency. A 2'-methoxy group provided intermediate potency as an antagonist while enhancing agonist activity. An N1-methyl analogue was a weak antagonist with no agonist activity. An 8-bromo substitution and replacement of the N6-amino group with methylthio, chloro, or hydroxy groups greatly reduced the ability to interact with P2Y1 receptors. Benzoylation or dimethylation of the N6-amino group also abolished or greatly diminished the antagonist activity. In summary, our results further define the structure-activity of adenosine bisphosphates as P2Y1 receptor antagonists and have led to the identification of the most potent antagonist reported to date for this receptor.
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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.