title: RADIOLABELING AND EFFICIENT SYNTHESIS OF TRITIATED 2-CHLORO-N6-(3-IODOBENZYL)ADENOSINE-5'-N-METHYLURON-AMIDE, A POTENT, SELECTIVE A3ADENOSINE RECEPTOR AGONIST.
abstract: We recently reported that 2-substitution ofN6-benzyladenosine-5'-uronamides greatly enhances selectivity of agonists for rat A3adenosine receptorsJ. Med. Chem.1994,37, 3614-3621). Specifically, 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (2-CI-IB-MECA), which displayed aK1value of 0.33 nM, is the most selective for A3receptors yet reported with selectivity versus A1and A2areceptors of 2500- and 1400-fold, respectively. In order to obtain pharmacological tools for the study of A3adenosine 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 heatingN6-(3-iodobenzyl)-2-chloro-2',3'-di-O-acetyl-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%.
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 20892.
authors.forename: Hea O
authors.initials: HO
authors.lastname: Kim
authors.forename: Calvin
authors.initials: C
authors.lastname: Hawes
authors.forename: Pat
authors.initials: P
authors.lastname: Towers
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
keywords: Adenosine Derivatives; Adenosine Receptors; Nucleosides; Radioligands; Tritium