Radiolabeling and efficient synthesis of tritiated 2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methyluron-amide, a potent, selective A3 adenosine receptor agonist

✍ Scribed by H.O. Kim; C. Hawes; P. Towers; K.A. Jacobson

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 599 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199606)38:6<547::aid-jlcr870>3.0.co;2-y

✦ Synopsis

We recently reported that 2-substitution of M-benzyladenosine-5'-uronamides greatly enhances selectivity of agonists for rat A, adenosine receptors (J. Med. Chem. 1994, 37, 3614-3621). Specifically, 2-Chloro-M-(3-iodobenzyl)adenosine-5'-Nmethyluronamide (2-CI-IB-MECA), which displayed a K, 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 (1 2) in six steps with an overail yield of 5.6 %. Tritium was introduced in the penultimate step by heating NG-(3-iodobenzyl)-2-chloro-2',3'-di-Oacetyl-5'-(methoxycarbonyl)adenosine (17) with [3H]methylamine in methanol at 60 "C for 2 h. The specific activity of [3H]2-CI-IB-MECA was 29 Ci/mmol with a radiochemical purity of 99%.