1386935-79-0Relevant academic research and scientific papers
Orally active adenosine A1 receptor agonists with antinociceptive effects in mice
Korboukh, Ilia,Hull-Ryde, Emily A.,Rittiner, Joseph E.,Randhawa, Amarjit S.,Coleman, Jennifer,Fitzpatrick, Brendan J.,Setola, Vincent,Janzen, William P.,Frye, Stephen V.,Zylka, Mark J.,Jin, Jian
experimental part, p. 6467 - 6477 (2012/09/22)
Adenosine A1 receptor (A1AR) agonists have antinociceptive effects in multiple preclinical models of acute and chronic pain. Although numerous A1AR agonists have been developed, clinical applications of these agents have been hampered by their cardiovascular side effects. Herein we report a series of novel A1AR agonists, some of which are structurally related to adenosine 5′-monophosphate (5′-AMP), a naturally occurring nucleotide that itself activates A 1AR. These novel compounds potently activate A1AR in several orthogonal in vitro assays and are subtype selective for A1AR over A2AAR, A2BAR, and A3AR. Among them, UNC32A (3a) is orally active and has dose-dependent antinociceptive effects in wild-type mice. The antinociceptive effects of 3a were completely abolished in A1AR knockout mice, revealing a strict dependence on A1AR for activity. The apparent lack of cardiovascular side effects when administered orally and high affinity (Ki of 36 nM for the human A1AR) make this compound potentially suitable as a therapeutic.
