ArticleJournal of medicinal chemistry2011
Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate δ-ester modifications as selective agonists of the P2Y(4) receptor.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 48 citations in OpenAlex.
- Mild and Chemoselective Triethylsilane-Mediated Debenzylation for Phosphate Synthesis.Organic letters · 2025Article
- Pharmacological characterization of P2Y receptor subtypes - an update.Purinergic signalling · 2024Review
- Age-related changes in P2Y receptor signalling in mouse cochlear supporting cells.The Journal of physiology · 2023Article
- Targeting the Conformational Change in ArnA Dehydrogenase for Selective Inhibition of Polymyxin Resistance.Biochemistry · 2023Article
- Structure-activity relationships of pyrimidine nucleotides containing a 5'-α,β-methylene diphosphonate at the P2YBioorganic & medicinal chemistry letters · 2021Article
- Update of P2Y receptor pharmacology: IUPHAR Review 27.British journal of pharmacology · 2020Review
- Analogs of the ATP-Sensitive Potassium (KATP) Channel Opener Cromakalim with in Vivo Ocular Hypotensive Activity.Journal of medicinal chemistry · 2016Article
- Nucleotides Acting at P2Y Receptors: Connecting Structure and Function.Molecular pharmacology · 2015Review
- Rapid synthesis of alkoxyamine hydrochloride derivatives from alkyl bromide andSynthetic communications · 2014Article
- 4-Alkyloxyimino derivatives of uridine-5'-triphosphate: distal modification of potent agonists as a strategy for molecular probes of P2Y2, P2Y4, and P2Y6 receptors.Journal of medicinal chemistry · 2014Article
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- P2Y2 receptor agonist with enhanced stability protects the heart from ischemic damage in vitro and in vivo.Purinergic signalling · 2013Article
- Pharmacological characterization of the P2 receptors profile in the podocytes of the freshly isolated rat glomeruli.American journal of physiology. Cell physiology · 2013Article
- 4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2YMedChemComm · 2013Article
- Structure-based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates.Journal of medicinal chemistry · 2013Review
- Probing GPCR structure: adenosine and P2Y nucleotide receptors.Methods in enzymology · 2013Article
- 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
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and 5'-tetraphosphate esters. P2Y(4) receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N(4)-alkyloxycytidine derivatives. OH groups on a terminal δ-glucose phosphoester of uridine 5'-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N(4)-(Phenylpropoxy)-CTP 16 (MRS4062), Up(4)-[1]3'-deoxy-3'-fluoroglucose 34 (MRS2927), and N(4)-(phenylethoxy)-CTP 15 exhibit ≥10-fold selectivity for human P2Y(4) over P2Y(2) and P2Y(6) receptors (EC(50) values 23, 62, and 73 nM, respectively). δ-3-Chlorophenyl phosphoester 21 of Up(4) activated P2Y(2) but not P2Y(4) receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y(2) and P2Y(4) receptor models indicated greater steric tolerance of N(4)-phenylpropoxy group at P2Y(4). Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y(4) receptor-selective agonists.
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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.