Novel nucleotide triphosphates as potent P2Y2 agonists with enhanced stability over UTP.
The synthesis of a series of novel C-linked nucleotide triphosphates is reported. These exhibit excellent agonist potency and selectivity for the P2Y2 receptor with a number of examples having EC50 values below 10 nM. Representative compounds from the N-linked and C-linked series showed enhanced metabolic stability compared with that of the natural ligand UTP.
Davenport
Richard J
RJ
UCB-Group, Granta Park, Abington, Cambridge CB1 6GS, UK. richard.davenport@ucb-group.com
Diaz
Paloma
P
Galvin
Frances C A
FC
Lloyd
Steve
S
Mack
Stephen R
SR
Owens
Ray
R
Sabin
Verity
V
Wynn
Joanne
J
D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D011994:Recombinant Proteins; D013056:Spectrophotometry, Ultraviolet; D014544:Uridine Triphosphate / Q000737:chemistry* / Q000494:pharmacology
D007202:Indicators and Reagents; D008024:Ligands; D009711:Nucleotides; C546385:P2RY2 protein, human; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D011994:Recombinant Proteins; D014544:Uridine Triphosphate