8-(SULFOSTYRYL)XANTHINES - WATER-SOLUBLE A(2A)-SELECTIVE ADENOSINE RECEPTOR ANTAGONISTS

8-(Sulfostyryl)xanthine derivatives were synthesized as water-soluble A(2A)-selective adenosine receptor (AR) antagonists, meta- and para-su lfostyryl-DMPX (3,7-dimethyl-1-propargylxanthine) derivatives 11a and 11b exhibited high affinity to rat AZA-AR in submicromolar concentrati ons, and were 20- to 30-fold selective versus rat A(1)-AR. Styryl-DMPX derivatives were inactive at human A(2B)- and A(3)-AR. 1,3-Dipropyl-8 -p-sulfostyrylxanthine (13) and its 7-methyl derivative (14) showed si milar (13) or higher (14) A(2A) affinity than 11a and 11b but showed n o (13) or only a low degree (14) of selectivity versus A(1)-, A(2B)-, and A(3)-AR. The A(2A)-selective sulfostyryl-DMPX derivatives exhibit high water-solubility and may be useful research tools for in vivo stu dies. (C) 1998 Elsevier Science Ltd. All rights reserved.