107337-70-2Relevant academic research and scientific papers
Pyrimidine nucleotides with 4-alkyloxyimino and terminal tetraphosphate δ-ester modifications as selective agonists of the P2Y4 receptor
Maruoka, Hiroshi,Jayasekara, M. P. Suresh,Barrett, Matthew O.,Franklin, Derek A.,De Castro, Sonia,Kim, Nathaniel,Costanzi, Stefano,Harden, T. Kendall,Jacobson, Kenneth A.
scheme or table, p. 4018 - 4033 (2011/08/05)
P2Y2 and P2Y4 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. P2Y4 receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N4-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. N4-(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 P2Y4 over P2Y2 and P2Y6 receptors (EC 50 values 23, 62, and 73 nM, respectively). δ-3-Chlorophenyl phosphoester 21 of Up4 activated P2Y2 but not P2Y 4 receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y2 and P2Y4 receptor models indicated greater steric tolerance of N4-phenylpropoxy group at P2Y4. Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y4 receptor-selective agonists.
Small ligands interacting with the phosphotyrosine binding pocket of the Src SH2 protein
Deprez, Pierre,Mandine, Eliane,Gofflo, Dominique,Meunier, Stephane,Lesuisse, Dominique
, p. 1295 - 1298 (2007/10/03)
Various small fragments bearing phosphate, phosphonate or phosphonic acid moieties have been prepared through parallel synthesis and their binding potencies evaluated on the Src SH2 protein using a BIAcore assay. This provided us insight into the requirement of the Src SH2 pTyr binding pocket and some promising small ligands have been characterised.
