Abstract
8-(Sulfostyryl)xanthine derivatives were synthesized as water-soluble A2A-selective adenosine receptor (AR) antagonists. meta- and para-sulfostyryl-DMPX (3,7-dimethyl-1-propargylxanthine) derivatives 11a and 11b exhibited high affinity to rat A2A-AR in submicromolar concentrations, and were 20- to 30-fold selective versus rat A1-AR. Styryl-DMPX derivatives were inactive at human A2B- and A3-AR. 1,3-Dipropyl-8-p-sulfostyrylxanthine (13) or only a 7-methyl derivative (14) showed similar (13) or higher (14) A2A affinity than 11a and 11b but showed no (13) or only a low degree (14) of selectivity versus A1-, A2B-, and A3-AR. The A2A-selective sulfostyryl-DMPX derivatives exhibit high water-solubility and may be useful research tools for in vivo studies.
MeSH terms
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Animals
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Arylsulfonic Acids / chemical synthesis*
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Arylsulfonic Acids / chemistry
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Arylsulfonic Acids / metabolism
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Arylsulfonic Acids / pharmacology
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CHO Cells
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Central Nervous System Stimulants / chemical synthesis*
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Central Nervous System Stimulants / chemistry
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Central Nervous System Stimulants / metabolism
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Central Nervous System Stimulants / pharmacology
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Cerebral Cortex / metabolism
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Cricetinae
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Humans
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Hydrogen-Ion Concentration
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Magnetic Resonance Spectroscopy
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Purinergic P1 Receptor Antagonists*
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Radioligand Assay
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Rats
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Receptor, Adenosine A2A
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Receptors, Purinergic P1 / biosynthesis
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / biosynthesis
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Solubility
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Structure-Activity Relationship
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Styrenes / chemical synthesis*
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Styrenes / chemistry
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Styrenes / metabolism
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Styrenes / pharmacology
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Xanthines / chemical synthesis*
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Xanthines / chemistry
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Xanthines / metabolism
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Xanthines / pharmacology
Substances
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Arylsulfonic Acids
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Central Nervous System Stimulants
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Purinergic P1 Receptor Antagonists
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Receptor, Adenosine A2A
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Receptors, Purinergic P1
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Recombinant Proteins
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Styrenes
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Xanthines