Synthesis and P2Y2 receptor agonist activities of uridine 5′-phosphonate analogues
| Autor: | Davy Sinnaeve, Kenneth A. Jacobson, Sara Van Poecke, José C. Martins, T. Kendall Harden, Serge Van Calenbergh, T. Santhosh Kumar, Matthew O. Barrett |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Agonist
P2Y receptor Stereochemistry medicine.drug_class Organic Chemistry Clinical Biochemistry Allosteric regulation Pharmaceutical Science Biochemistry Phosphonate Uridine chemistry.chemical_compound chemistry Purinergic P2Y Receptor Agonists Drug Discovery medicine Molecular Medicine Molecular Biology Uracil nucleotide Uridine triphosphate |
| DOI: | 10.17615/h0n1-4d70 |
| Popis: | We explored the influence of modifications of uridine 5'-methylenephosphonate on biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a series of 5-substituted uridine 5'-methylenephosphonates were the reaction of a suitably protected uridine 5'-aldehyde with [(diethoxyphosphinyl)methylidene]triphenylphosphorane, C-5 bromination and a Suzuki-Miyaura coupling. These analogues behaved as selective agonists at the P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y(2) receptor. |
| Databáze: | OpenAIRE |
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