Title:Apixaban: A New Player in the Anticoagulant Class
Volume: 13
Issue: 6
Author(s): Ritesh Agrawal, Pratima Jain and S. N. Dikshit
Affiliation:
Keywords:
Apixaban, anticoagulant, BMS-562247-01, Eliquis®, factor X (FXa), fXa, Factor Xa Inhibitors, MOLECULAR CHEMISTRY, patent, RECEPTOR INTERACTION
Abstract: Apixaban (BMS-562247-01) is a compound being investigated as an anticoagulant. Apixaban molecule is
developed in a joint venture by Pfizer and Bristol-Myers Squibb. Apixaban, a coagulation factor Xa inhibitor, approved in
the E.U. in 2011 for the prevention of venous thromboembolic events in adult patients, who have undergone elective hip
or knee replacement. The Apixaban based drug will be marketed under the brand name Eliquis® and is expected to rack
up annual sales of over $2.5 billion. Apixaban is expected to provide stiff competition to warfarin, a popular blood thinner
used in Europe. Warfarin is known to cause some serious side effects in patients. Apixaban, as compared with aspirin,
reduced the risk of stroke or systemic embolism in patients experiencing atrial fibrillation by more than 50% (from 3.7%
per annum with aspirin to 1.6% per annum with apixaban). Apixaban exhibits superiority to enoxaparin in preventing
thrombosis in patients undergoing elective hip replacement surgery with similar bleeding rates. Apixaban is a highly
selective and potent Factor Xa Inhibitor with Ki=0 8nM to both free as well as prothrombinase bound FXa. In X-ray
crystal structure studies indicate that the pyrazole N-2 nitrogen atom interacts with backbone of Gln192 and the carbonyl
oxygen of carboxamide interacts with NH of Gly216. The orientation of phenyllactum in the S4 region indiacates an edge
to face interaction with Trp215, which is positioned between the Tyr99 and Phe174. In the present review, we have tried
to cover comparative study of various FXa-inhibitors and point out apixaban in the various aspect including molecular
chemistry, physical properties, commercial synthesis, current patent status, crystalline polymorphic forms, molecular
receptor interaction, pharmacophore rational, mechanism of action, clinical studies, preclinical, adverse effect, available
formulation, dose regimen and co-therapy, thus giving emphasis on medicinal chemistry aspects.
