Synthesis and structure-activity relationship of uracil nucleotide derivatives towards the identification of human P2Y6 receptor antagonists.
作者： Diana Meltzer , Ophir Ethan , Guillaume Arguin , Yael Nadel , Ortal Danino
DOI: 10.1016/J.BMC.2015.07.004
关键词:
摘要: P2Y6 receptor (P2Y6-R) is involved in various physiological and pathophysiological events. With a view to set rules for the design of UDP-based reversible P2Y6-R antagonists as potential drugs, we established structure-activity relationship UDP analogues, bearing modifications at uracil ring, ribose moiety, phosphate chain. For instance, C5-phenyl- or 3-NMe-uridine-5'-α,β-methylene-diphosphonate, 16 23, lack 2'-OH, 12-15, resulted loss both agonist antagonist activity toward hP2Y6-R. However, uridylyl phosphosulfate, 19, selectively inhibited hP2Y6-R (IC50 112 μM) versus P2Y2/4-Rs. In summary, have comprehensive SAR ligands towards development antagonists.
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