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The syntheses and in vitro biotransformation studies of [ 14 C]apixaban, a highly potent, selective, efficacious and orally bioavailable inhibitor of blood coagulation Factor Xa
Author(s) -
Maxwell Brad D.,
Tran Scott B.,
Chen ShiangYuan,
Zhang Donglu,
Chen BangChi,
Zhang Huiping,
Bonacorsi Samuel J.
Publication year - 2011
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1890
Subject(s) - chemistry , apixaban , bioavailability , coagulation , biotransformation , in vitro , pharmacology , rivaroxaban , stereochemistry , biochemistry , enzyme , medicine , warfarin , atrial fibrillation
Apixaban is a potent inhibitor of blood coagulation Factor Xa in the late stages of development. [ 14 C]apixaban was synthesized with the 14C label in the two different lactam ring systems within the molecule for various in vitro and in vivo metabolism studies. A nine‐step synthesis of [ 14 C]apixaban, 10 , with the label in the central lactam ring was completed in 14% overall yield. A second synthesis of [ 14 C]apixaban, 14 , with the 14C label in the outer lactam ring was completed in three steps in a 14% overall yield. No significant differences were observed between the metabolite profiles of 10 and 14 , [ 14 C]apixaban, from both rat and human hepatocyte or microsomal incubations. Copyright © 2011 John Wiley & Sons, Ltd.