Solubilities of adenosine antagonists determined by radioreceptor assay

The practical use of many adenosine receptor antagonists is limited by poor aqueous solubility. In some cases, solubilities are so low that they are difficult to measure by conventional means. To determine solubilities of adenosine antagonists, a sensitive radioreceptor method has been developed. Solubilities in Tris buffer (pH 7.7) ranged from 141 nM for 8-(2-amino-4-chlorophenyl)-1,3-dipropylxanthine to 945 microM for the amino-substituted xanthine PD 113,297. Ratios between solubility and adenosine receptor affinity varied from 15.8 for the A2-selective antagonist HTQZ to 169,000 for PD 113,297. From literature data on functional activity, it is apparent that useful adenosine antagonist activity in-vivo is only seen in compounds with solubility/affinity ratios greater than 100.