The reduction of 1-allyl-8-cyclopentyl-3-(3-fluoropropyl)xanthine, 7, with tritium gas catalyzed by 10% Pd-C gave 8-cyclopentyl-3-(3-fluoropropyl)-1-[2,3-3 H]propylxanthine ([ 3 H]CPFPX), 8*, a potent and selective antagonist for the A 1 adenosine receptor (A 1 AR). The synthesis of 7 proceeded from 6aminouracil, 1, which underwent silylation and alkylation with allyl bromide to form 6-amino-3-allyluracil, 2. Nitrosation led to the 5-nitroso compound, 3, which underwent reduction to the 4,5-diaminouracil, 4, and carbodiimidemediated acylation with cyclopentanecarboxylic acid produced 3-allyl-6amino-5-cyclopentylcarboxamidouracil, 6. Alkylation at NÀ1 with 3-fluoro-1-bromopropane and cyclization with alkali completed the synthesis of 7.
[ 3 H]CPFPX had a radiochemical purity of > 98% and a specific activity of >2.1 TBq/mmol (57 Ci / mmol). [ 3 H]CPFPX bound to the rat, pig and human A 1 AR with a K D of 0.63, 1.37 and 0.71 nM, respectively. The K D at the rat and human A 2A AR was 812 and 940 nM, respectively, thus giving selectivities of >1200-and >700-fold.