The syntheses and in vitro biotransformation studies of [14C]apixaban, a highly potent, selective, efficacious and orally bioavailable inhibitor of blood coagulation Factor Xa

✍ Scribed by Brad D. Maxwell; Scott B. Tran; Shiang-Yuan Chen; Donglu Zhang; Bang-Chi Chen; Huiping Zhang; Samuel J. Bonacorsi Jr

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 223 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1890

✦ Synopsis

Abstract

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.