RADIOLABELING AND EFFICIENT SYNTHESIS OF TRITIATED 2-CHLORO--(3-IODOBENZYL)ADENOSINE-5'--METHYLURON-AMIDE, A POTENT, SELECTIVE A ADENOSINE RECEPTOR AGONIST.

We recently reported that 2-substitution of -benzyladenosine-5'-uronamides greatly enhances selectivity of agonists for rat A adenosine receptors , , 3614-3621). Specifically, 2-Chloro--(3-iodobenzyl)adenosine-5'--methyluronamide (2-CI-IB-MECA), which displayed a value of 0.33 nM, is the most selective for A receptors yet reported with selectivity versus A and A receptors of 2500- and 1400-fold, respectively. In order to obtain pharmacological tools for the study of A adenosine receptors, two routes for radiolabeling of 2-CI-IB-MECA through incorporation of tritium at the 5'-methylamido group were compared. One route formed a 2',3'-protected nucleoside 5'-carboxylic acid (9), which was condensed with methylamine and deprotected. The more efficient synthesis started from D-ribose and provided 2-CI-IB-MECA (12) in six steps with an overall yield of 5.6 %. Tritium was introduced in the penultimate step by heating -(3-iodobenzyl)-2-chloro-2',3'-di--acetyl-5'-(methoxycarbonyl)adenosine with [H]methylamine in methanol at 60 °C for 2 h. The specific activity of [H]2-CI-IB-MECA was 29 Ci/mmol with a radiochemical purity of 99%.