Journal ArticleDOI
Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists.
Kenneth A. Jacobson,Carola Gallo-Rodriguez,Neli Melman,Bilha Fischer,Michel Maillard,Andrew van Bergen,Philip J. M. van Galen,Yishai Karton +7 more
TLDR
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) and 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl) xanthines was a potent and very A2Abstract:
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.read more
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Journal Article
Nomenclature and classification of purinoceptors
Bertil B. Fredholm,Maria P. Abbracchio,Geoffrey Burnstock,J. W. Daly,T K Harden,Kenneth A. Jacobson,P Leff,Michael Williams +7 more
TL;DR: The evidence is now compelling that ATP plays important physiological and/ or pathophysiological roles in a variety of biological systems, and the presence of receptors for ADP and adenosine (presumably A2) receptors exist on platelets is compelling.
Journal ArticleDOI
International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update
TL;DR: In the 10 years since the previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors, no developments have led to major changes in the recommendations, but there have been so many other developments that an update is needed.
Journal ArticleDOI
Recent developments in adenosine receptor ligands and their potential as novel drugs
TL;DR: Medicinal chemical approaches have been applied to all four of the adenosine receptor (AR) subtypes to create selective agonists and antagonists for each to facilitate research on therapeutic applications of modulating the ARs and in some cases has provided clinical candidates.
Journal ArticleDOI
Palladium(II)-catalyzed oxidative C-H/C-H cross-coupling of heteroarenes.
TL;DR: An efficient methodology for the synthesis of unsymmetrical biheteroaryl molecules has been developed via Pd(II)-catalyzed oxidative C-H/C-H cross-coupling of heteroarenes via an inversion in reactivity and selectivity.
Journal ArticleDOI
Pharmacology of adenosine A2A receptors
Ennio Ongini,Bertil B. Fredholm +1 more
TL;DR: In this review, Ennio Ongini and Bertil Fredholm describe how recently developed potent and selective A2A receptor antagonists can be used to delineate the physiological and pathological processes regulated by A 2A receptors.
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