Structure
Warfarin is a synthetic coumarin derivative with a 4-hydroxycoumarin core structure substituted with a 3-phenylpropyl side chain.
Chemical Formula: C₁₉H₁₆O₄
Mode of Action
Vitamin K Epoxide Reductase Inhibition: Blocks the enzyme vitamin K epoxide reductase, preventing the regeneration of reduced vitamin K.
Coagulation Factor Inhibition: Reduces the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X.
Anticoagulant Effect: Prolongs clotting times (INR) to prevent thrombosis and embolism.
Uses
Prophylaxis and Treatment of Thromboembolic Disorders: Prevents deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke.
Atrial Fibrillation: Reduces the risk of stroke by preventing clot formation.
Mechanical Heart Valves: Prevents thrombus formation on artificial valves.
Myocardial Infarction: Lowers the risk of recurrent heart attacks by preventing clot formation.
Structure-Activity Relationship (SAR)
Coumarin Core: Essential for binding to vitamin K epoxide reductase.
3-Phenylpropyl Side Chain: Enhances binding affinity and specificity for the target enzyme.
Hydroxyl Group: Increases solubility and facilitates hydrogen bonding with the enzyme.
Substituents: Modifications on the phenyl ring can affect potency, metabolism, and duration of action.
Synthesis of Warfarin
Warfarin is synthesized through the condensation of 4-hydroxycoumarin with 3-phenyl-2-propenal (chalcone).
Synthetic Route:
Starting Materials: 4-Hydroxycoumarin and 3-phenyl-2-propenal.
Condensation Reaction: Under basic conditions, perform an aldol condensation to form the warfarin structure.
Purification: Isolate warfarin through crystallization and recrystallization processes.
Reaction Scheme:
4-Hydroxycoumarin + 3-Phenyl-2-propenal → Warfarin