STRUCTURE-ACTIVITY-RELATIONSHIPS OF 8-CYCLOALKYL-1,3-DIPROPYLXANTHINES AS ANTAGONISTS OF ADENOSINE RECEPTORS

8-Substituted xanthines currently represent the most potent class of adenosine-receptor antagonists. A series of 8-substituted 1,3-dipropylxanthines was prepared and their potency as antagonists of A1and A2 adenosine receptors of human platelets and rat adipocytes, respectively, were determined. No agents studied were as potent as 8-cyclopentyl-l,3-dipropylxanthine as antagonists of the A1 adenosine receptor, but 8-(2-methylcyclopropyl)-l,3-dipropylxanthine was at least 1000-fold more potent as an antagonist of A1than of A2 adenosine receptors. While most substitutions on the 8-cycloalkyl moiety caused decreased potency to inhibit both A1and A2 adenosine receptors, 8-[trans-4-(acetamidomethyl)cyclohexyl]-l,3-dipropylxanthine was nearly equipotent as an antagonist of the two receptors and appeared to be the most potent antagonist of A2 adenosine receptors reported to date. © 1990, American Chemical Society. All rights reserved.