Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists
Citations Over TimeTop 10% of 1993 papers
Abstract
A series of substituted 8-styryl derivatives of 1,3,7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues. 1,3-Dimethylxanthine derivatives tended to be more selective for A2-receptors than the corresponding 1,3-diallyl, diethyl, or dipropyl derivatives. Substitutions of the phenyl ring at the 3-(monosubstituted) and 3,5-(disubstituted) positions were favored. 1,3, 7-Trimethyl-8-(3-chlorostyryl)xanthine was a moderately potent (Ki vs [3H]CGS 21680 was 54 nM) and highly A2-selective (520-fold) adenosine antagonist. 1,3,7-Trimethyl-8-[(3-carboxy-1-oxopropyl)amino] styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM). 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl) xanthine was a potent (Ki = 24 nM) and very A2-selective (110-fold) adenosine antagonist.
Related Papers
- → History of the Icon programming language(1996)25 cited
- → Basic Types of Correlation between Text and Icon, between Verbal and Visual Icons(2006)5 cited
- Susquehanna Chorale Spring Concert "Roots and Wings"(2017)
- → Icon «The Judgment of the Jews over Christ» of the First Half of the XIX Century(2020)
- → A new discovery. The icon of «St. Sergius, Nikon and Savva»(2022)