ArticleJournal of medicinal chemistry2006
Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor.
Article in Journal of medicinal chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 70 citations in OpenAlex.
- An updated review of enantioselective syntheses and biological actions of carbanucleosides.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Pyrimidinergic P2Y1-Like Nucleotide Receptors Are Functional in Rat Conjunctival Goblet Cells.Investigative ophthalmology & visual science · 2025Article
- Pharmacological characterization of P2Y receptor subtypes - an update.Purinergic signalling · 2024Review
- Stereocontrolled access to thioisosteres of nucleoside di- and triphosphates.Nature chemistry · 2024Article
- Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures.Nature communications · 2023Article
- Article
- Structure activity relationship of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives as P2YBioorganic & medicinal chemistry letters · 2021Article
- Pyrimidine Nucleotides Containing a (S)-Methanocarba Ring as P2YMedChemComm · 2017Article
- Thymidine 5'-O-monophosphorothioate induces HeLa cell migration by activation of the P2Y6 receptor.Purinergic signalling · 2016Article
- Article
- Article
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- 4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2YMedChemComm · 2013Article
- AMP-activated protein kinase as regulator of P2Y(6) receptor-induced insulin secretion in mouse pancreatic β-cells.Biochemical pharmacology · 2013Article
- Purinergic receptors regulate myogenic tone in cerebral parenchymal arterioles.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Probing GPCR structure: adenosine and P2Y nucleotide receptors.Methods in enzymology · 2013Article
- Radical-translocation intermediates and hurdling of pathway defects in "super-oxidized" (Mn(IV)/Fe(IV)) Chlamydia trachomatis ribonucleotide reductase.Journal of the American Chemical Society · 2012Article
- Molecular Structure of P2Y Receptors: Mutagenesis, Modeling, and Chemical Probes.Wiley interdisciplinary reviews. Membrane transport and signaling · 2012Article
- P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential.CNS & neurological disorders drug targets · 2012Review
- G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions.Purinergic signalling · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
The structure-activity relationships and molecular modeling of the uracil nucleotide activated P2Y6 receptor have been studied. Uridine 5'-diphosphate (UDP) analogues bearing substitutions of the ribose moiety, the uracil ring, and the diphosphate group were synthesized and assayed for activity at the human P2Y6 receptor. The uracil ring was modified at the 4 position, with the synthesis of 4-substituted-thiouridine 5'-diphosphate analogues, as well as at positions 2, 3, and 5. The effect of modifications at the level of the phosphate chain was studied by preparing a cyclic 3',5'-diphosphate analogue, a 3'-diphosphate analogue, and several dinucleotide diphosphates. 5-Iodo-UDP 32 (EC50 = 0.15 microM) was equipotent to UDP, while substitutions of the 2'-hydroxyl (amino, azido) greatly reduce potency. The 2- and 4-thio analogues, 20 and 21, respectively, were also relatively potent in comparison to UDP. However, most other modifications greatly reduced potency. Molecular modeling indicates that the beta-phosphate of 5'-UDP and analogues is essential for the establishment of electrostatic interactions with two of the three conserved cationic residues of the receptor. Among 4-thioether derivatives, a 4-ethylthio analogue 23 displayed an EC50 of 0.28 microM, indicative of favorable interactions predicted for a small 4-alkylthio moiety with the aromatic ring of Y33 in TM1. The activity of analogue 19 in which the ribose was substituted with a 2-oxabicyclohexane ring in a rigid (S)-conformation (P = 126 degrees , 1'-exo) was consistent with molecular modeling. These results provide a better understanding of molecular recognition at the P2Y6 receptor and will be helpful in designing selective and potent P2Y6 receptor ligands.
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.