819837-70-2Relevant academic research and scientific papers
Development of spin-labeled probes for adenosine receptors
Ila?, Janez,Pe?ar, Slavko,Hockemeyer, J?rg,Euler, Harald,Kirfel, Armin,Müller, Christa E.
, p. 2108 - 2114 (2005)
Functionalized xanthine derivatives bearing a nitroxide moiety at the 3- or 8-position were synthesized as electron paramagnetic resonance (EPR) probes. The 8-cyclopentyl-1-propylxanthine derivative 4, spin-labeled at N3 by substitution with a nitroxide-bearing dihydropyrrole moiety, was a potent and selective A1 adenosine receptor antagonist (Ki for A 1 5.5 nM, 1600-fold selectivity vs A2A, > 200-fold vs A2B, and 310-fold vs A3 adenosine receptors). 8-(1-Oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)-1,3-dipropylxanthine 10 (Ki for A1 8.2 nM) was similarly potent and selective, while 8-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-1,3-dipropylxanthine 11 (Ki for A1 160 nM) exhibited significantly lower affinity for A1 adenosine receptors. 8-[4-(((1-Oxyl-2,2,6,6- tetramethylpiperidin-4-yl)amino)-2-oxoethoxy)phenyl]-1-propylxanthine 14, a 3-unsubstituted xanthine derivative, was found to be a potent A2B adenosine receptor antagonist (Ki for A2B 48 nM) but also exhibited high affinity for A1 receptors (Ki for A 1 15.7 nM). An X-ray structure of compound 10 was obtained, confirming the proposed structure. The novel spin-labeled A1- selective or A1/A2B-nonselective adenosine receptor antagonists may become useful probes for biophysicochemical investigations of adenosine receptors in their membrane environment.
