Tritium‐labelled 8‐cyclopentyl‐3‐(3‐fluoropropyl)‐1‐propylxanthine ([ 3 H]CPFPX), a potent and selective antagonist for the A 1 adenosine receptor

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 6‐aminouracil, 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 carbodiimide‐mediated acylation with cyclopentanecarboxylic acid produced 3‐allyl‐6‐amino‐5‐cyclopentylcarboxamidouracil, 6 . Alkylation at N −1 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. Copyright © 2003 John Wiley & Sons, Ltd.