1160271-20-4Relevant academic research and scientific papers
The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14
Gauthier, Jacques Yves,Belley, Michel,Deschênes, Denis,Fournier, Jean-Fran?ois,Gagné, Sébastien,Gareau, Yves,Hamel, Martine,Hénault, Martin,Hyjazie, Huda,Kargman, Stacia,Lavallée, Geneviève,Levesque, Jean-Fran?ois,Li, Lianhai,Mamane, Ya?l,Mancini, Joseph,Morin, Nicolas,Mulrooney, Erin,Robichaud, Jo?l,Thérien, Michel,Tranmer, Geoffrey,Wang, Zhaoyin,Wu, Jin,Black, W. Cameron
scheme or table, p. 2836 - 2839 (2011/06/24)
A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY 14 with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the electron-withdrawing nature of the substituents markedly reduced glucuronidation and improved the pharmacokinetic profile. Additional optimization led to the identification of compound 38 which is an 8 nM UDP-competitive antagonist of P2Y14 with a good pharmacokinetic profile.
