RADIOLABELING AND EFFICIENT SYNTHESIS OF TRITIATED O-N-6(3-IODOBENZYL)ADENOSINE-5'-N-METHYLURONAMIDE, A POTENT, SELECTIVE A(3) ADENOSINE RECEPTOR AGONIST
Ho. Kim et al., RADIOLABELING AND EFFICIENT SYNTHESIS OF TRITIATED O-N-6(3-IODOBENZYL)ADENOSINE-5'-N-METHYLURONAMIDE, A POTENT, SELECTIVE A(3) ADENOSINE RECEPTOR AGONIST, Journal of labelled compounds & radiopharmaceuticals, 38(6), 1996, pp. 547-560
Citations number
14
Categorie Soggetti
Chemistry Analytical","Pharmacology & Pharmacy","Biochemical Research Methods
We recently reported that 2-substitution of N-6-benzyladenosine-5'-uro
namides greatly enhances selectivity of agonists for rat A, adenosine
receptors (J. Med. Chem. 1994, 37, 3614-3621). Specifically, -N-6-(3-i
odobenzyl)adenosine-5'-N-methyluron-amide (2-Cl-IB-MECA), which displa
yed a K-l value of 0.33 nM, is the most selective for A(3) receptors y
et reported with selectivity versus A(1) and A(2a) receptors of 2500-
and 1400-fold, respectively. In order to obtain pharmacological tools
for the study of A(3) adenosine receptors, two routes for radiolabelin
g of 2-Cl-IB-MECA through incorporation of tritium at the 5'-methylami
do group were compared. One route formed a 2',3'-protected nucleoside
5'-carboxylic acid (9), which was condensed with methylamine and depro
tected. The more efficient synthesis started from D-ribose and provide
d 2-Cl-IB-MECA (12) in six steps with an overall yield of 5.6%. Tritiu
m was introduced in the penultimate step by heating l)-2-chloro-2',3'-
di-O-acetyl-5'-(methoxycarbonyl) adenosine (17) with [H-3]methylamine
in methanol at 60 degrees C for 2 h. The specific activity of [H-3]2-C
l-IB-MECA was 29 Ci/mmol with a radiochemical purity of 99%.