Apixaban , ≥99% , 503612-47-3

CAS NO.：503612-47-3

Empirical Formula: C25H25N5O4

Molecular Weight: 459.5

MDL number: MFCD11977295

EINECS: 639-684-6

PRODUCT Properties

• Melting point: 235-238°C
• Boiling point: 770.5±60.0 °C(Predicted)
• Density: 1.42
• storage temp.: Refrigerator
• solubility: DMSO (Slightly, Heated), Methanol (Slightly)
• pka: 15.01±0.20(Predicted)
• form: Solid
• color: White to Off-White
• InChIKey: QNZCBYKSOIHPEH-UHFFFAOYSA-N
• SMILES: C1(=O)N(C2=CC=C(N3CCCCC3=O)C=C2)CCC2C(C(N)=O)=NN(C3=CC=C(OC)C=C3)C1=2

Description and Uses

Eliquis (apixaban), a direct inhibitor of factor Xa (FXa), was approved by the European Commission on May 18, 2011 for prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. The discovery of apixaban was the culmination of a succession of novel and innovative medicinal chemistry discoveries starting with the identification of nonpeptide leads, rational drug design using computer-aided and X-ray crystallographic information, and the building of drug-like properties through the systematic replacement of basic groups with neutral moieties. Apixaban arose from modifications to razaxaban by constraining a pyrazole amide to form a bicyclic pyrazolo-pyridinone scaffold. Optimization of the P1 group resulted in the identification of the nonbasic methoxy phenyl group, while a P4 piperidinone improved the balance of potency and pharmacokinetics with low Vdss. The synthesis of apixaban begins with the generation of a hydrazone of 4-methoxyaniline which is then used in a 3+2 cycloaddition with a dihydropiperidinone to form a bicyclic pyrazolo-pyridinone scaffold. The distal piperidinone group is installed using an Ullmann coupling reaction followed by aminolysis of an ethyl ester on the pyrazole ring to complete the synthesis of apixaban.

Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively.

Safety

• Symbol(GHS): GHS08
• Signal word: Warning
• Hazard statements: H361
• Precautionary statements: P501-P202-P201-P280-P308+P313-P405