72503-96-9Relevant articles and documents
5-Substituted UTP derivatives as P2Y2 receptor agonists
Knoblauch, Bernd H.A.,Mueller, Christa E.,Jaerlebark, Leif,Lawoko, Grace,Kottke, Thomas,Wikstroem, Martin A.,Heilbronn, Edith
, p. 809 - 824 (2007/10/03)
A series of 5-alkyl-substituted UTP derivatives, which had been synthesized previously with a moderate degree of purity, was resynthesized, purified, and characterized. Synthetic and purification procedures were optimized. New spectroscopic data, including 13C- and 31P NMR data, are presented. Phosphorylation reactions yielded a number of side products, such as the 2'-, 3'-, and 5'-monophosphates, the 2',3'-cyclic monophosphates, and the 2',3'-cyclic phosphates of the 5'-triphosphates. Furthermore, raw products were contaminated with inorganic phosphates, including cyclometatriphosphate, phosphate, and pyrophosphate. The uracil nucleotides were investigated for their potency to increase intracellular calcium concentrations by stimulation of P2Y2 receptors (P2Y2R) on NG108- 15 cells, a mouse neuroblastoma x glioma cell line, and in human basal epithelial airway cells, including a cystic fibrosis (CF/T43) cell line. UTP exhibited EC50 values of ca. 1 μM (in NG108-15 cells) and of 0.1 μM (in CF/T43 cells), respectively. 5-Substituted UTP derivatives were agonists at the P2Y2R, but were less potent than UTP. 5-Ethyl-UTP, for example, exhibited an EC50 value of 99 μM at P2Y2R of NG108-15 cells and proved to be a full agonist. With increasing volume of the 5- substituent of UTP derivatives, P2Y2 activity decreased.
