ArticleJournal of medicinal chemistry2000
Synthesis, biological activity, and molecular modeling of ribose-modified deoxyadenosine bisphosphate analogues as P2Y(1) receptor ligands.
Article in Journal of medicinal chemistry, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 129 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
- Pharmacological inhibition of host pathways enhances macrophage killing of intracellular bacterial pathogens.Microbiology spectrum · 2026Article
- Mild and Chemoselective Triethylsilane-Mediated Debenzylation for Phosphate Synthesis.Organic letters · 2025Article
- Burnstock and the legacy of the inhibitory junction potential and P2Y1 receptors.Purinergic signalling · 2021Review
- Demystifying P2YJournal of chemical information and modeling · 2017Article
- β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Comparative analysis of optogenetic actuators in cultured astrocytes.Cell calcium · 2014Article
- Modified diadenosine tetraphosphates with dual specificity for P2Y1 and P2Y12 are potent antagonists of ADP-induced platelet activation.Journal of thrombosis and haemostasis : JTH · 2012Article
- Molecular Structure of P2Y Receptors: Mutagenesis, Modeling, and Chemical Probes.Wiley interdisciplinary reviews. Membrane transport and signaling · 2012Article
- G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions.Purinergic signalling · 2012Review
- Resolution and concordance in dissecting the compound inhibitory junction potential.The Journal of physiology · 2012Article
- Development of a comprehensive set of P2 receptor pharmacological research compounds.Purinergic signalling · 2012Article
- Synthesis of cyclic adenosine 5'-diphosphate ribose analogues: a C2'endo/syn "southern" ribose conformation underlies activity at the sea urchin cADPR receptor.Organic & biomolecular chemistry · 2011Article
- Development of selective agonists and antagonists of P2Y receptors.Purinergic signalling · 2009Article
- Development of selective high affinity antagonists, agonists, and radioligands for the P2Y1 receptor.Combinatorial chemistry & high throughput screening · 2008Review
- Activation of P2Y1 nucleotide receptors induces inhibition of the M-type K+ current in rat hippocampal pyramidal neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy.Pharmacological reviews · 2006Review
- P2Y1 and P2Y2 receptor distribution varies along the human placental vascular tree: role of nucleotides in vascular tone regulation.The Journal of physiology · 2006Article
- (N)-methanocarba-2MeSADP (MRS2365) is a subtype-specific agonist that induces rapid desensitization of the P2Y1 receptor of human platelets.Journal of thrombosis and haemostasis : JTH · 2006Article
- [32P]2-iodo-N6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate ([32P]MRS2500), a novel radioligand for quantification of native P2Y1 receptors.British journal of pharmacology · 2006Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The structure-activity relationships of adenosine-3', 5'-bisphosphates as P2Y(1) receptor antagonists have been explored, revealing the potency-enhancing effects of the N(6)-methyl group and the ability to substitute the ribose moiety (Nandanan et al. J. Med. Chem. 1999, 42, 1625-1638). We have introduced constrained carbocyclic rings (to explore the role of sugar puckering), non-glycosyl bonds to the adenine moiety, and a phosphate group shift. The biological activity of each analogue at P2Y(1) receptors was characterized by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit its stimulation elicited by 30 nM 2-methylthioadenosine-5'-diphosphate (antagonist effect). Addition of the N(6)-methyl group in several cases converted pure agonists to antagonists. A carbocyclic N(6)-methyl-2'-deoxyadenosine bisphosphate analogue was a pure P2Y(1) receptor antagonist and equipotent to the ribose analogue (MRS 2179). In the series of ring-constrained methanocarba derivatives where a fused cyclopropane moiety constrained the pseudosugar ring of the nucleoside to either a Northern (N) or Southern (S) conformation, as defined in the pseudorotational cycle, the 6-NH(2) (N)-analogue was a pure agonist of EC(50) 155 nM and 86-fold more potent than the corresponding (S)-isomer. The 2-chloro-N(6)-methyl-(N)-methanocarba analogue was an antagonist of IC(50) 51.6 nM. Thus, the ribose ring (N)-conformation appeared to be favored in recognition at P2Y(1) receptors. A cyclobutyl analogue was an antagonist with IC(50) of 805 nM, while morpholine ring-containing analogues were nearly inactive. Anhydrohexitol ring-modified bisphosphate derivatives displayed micromolar potency as agonists (6-NH(2)) or antagonists (N(6)-methyl). A molecular model of the energy-minimized structures of the potent antagonists suggested that the two phosphate groups may occupy common regions. The (N)- and (S)-methanocarba agonist analogues were docked into the putative binding site of the previously reported P2Y(1) receptor model.
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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.