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Synfacts 2022; 18(12): 1377
DOI: 10.1055/s-0042-1753104
DOI: 10.1055/s-0042-1753104
Innovative Drug Discovery and Development
Synthesis of Coagulation Factor Xa Inhibitor Apixaban
Pinto DJ. P.
*
et al.
Bristol-Myers Squibb Company, Pennington, USA
Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa.
J. Med. Chem. 2007;
50: 5339-5356
DOI: 10.1021/jm070245n.
Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa.
J. Med. Chem. 2007;
50: 5339-5356
DOI: 10.1021/jm070245n.
Significance
Apixaban is an inhibitor of blood coagulation factor Xa (fXa), a serine protease that is crucial to the conversion of prothrombin into thrombin. The latter is the last enzyme in the coagulation cascade and is responsible for fibrin clot formation. Apixaban is used to treat and prevent blood clots. It is one of the current top ten blockbuster drugs.
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Comment
The synthesis of Apixaban features a Huisgen (3+2) cycloaddition/elimination sequence to form the pyrazole core. Ullman−Goldberg cross-coupling and subsequent aminolysis completes the synthesis of the inhibitor.
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Publication History
Article published online:
17 November 2022
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