A1 Refereed original research article in a scientific journal
Radiosynthesis of [(11)C]ximelagatran via palladium catalyzed [(11)C]cyanation
Authors: Airaksinen AJ, Andersson J, Truong P, Karlsson O, Halldin C
Publisher: WILEY-BLACKWELL
Publication year: 2008
Journal: Journal of Labelled Compounds and Radiopharmaceuticals
Journal name in source: JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
Journal acronym: J LABELLED COMPD RAD
Volume: 51
Issue: 1-2
First page : 1
Last page: 5
Number of pages: 5
ISSN: 0362-4803
DOI: https://doi.org/10.1002/jlcr.1461
Abstract
N-hydroxyamidines (amidoximes) may be used in prodrug technology in improving oral bioavailability of drugs containing amidino functional groups. In the body, amidoximes are reduced quickly to amidines by enzymes that are present in several organs. Ximelagatran is a benzamidoxime and ethyl ester prodrug of melagatran, which is a thrombin inhibitor. Our aim was to develop a fast and efficient labeling route for the synthesis of [(11)C]ximelagatran ([(11)C]3) with a label in a metabolically stable position. [(11)C]3 was synthesized via a two-step synthesis sequence, starting from palladium catalyzed [(11)C]cyanation of its corresponding bromide precursor (2-[2-(4-bromo-benzylcarbamoyl)-azetidin-1-yl]-1-cyclohexyl-2-oxoethyl amino-acetic acid ethyl ester) (1), followed by a reaction with hydroxylamine. [(11)C]3 was synthesized with 27 +/- 17% total overall decay corrected yield (specific radioactivity of 2360 +/- 165 Ci/mmol at EOS), with a total synthesis time of 45 min. A fast and efficient labeling route for the synthesis of [(11)C]3 was developed.
N-hydroxyamidines (amidoximes) may be used in prodrug technology in improving oral bioavailability of drugs containing amidino functional groups. In the body, amidoximes are reduced quickly to amidines by enzymes that are present in several organs. Ximelagatran is a benzamidoxime and ethyl ester prodrug of melagatran, which is a thrombin inhibitor. Our aim was to develop a fast and efficient labeling route for the synthesis of [(11)C]ximelagatran ([(11)C]3) with a label in a metabolically stable position. [(11)C]3 was synthesized via a two-step synthesis sequence, starting from palladium catalyzed [(11)C]cyanation of its corresponding bromide precursor (2-[2-(4-bromo-benzylcarbamoyl)-azetidin-1-yl]-1-cyclohexyl-2-oxoethyl amino-acetic acid ethyl ester) (1), followed by a reaction with hydroxylamine. [(11)C]3 was synthesized with 27 +/- 17% total overall decay corrected yield (specific radioactivity of 2360 +/- 165 Ci/mmol at EOS), with a total synthesis time of 45 min. A fast and efficient labeling route for the synthesis of [(11)C]3 was developed.
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