Warfarin

Warfarin is an oral anticoagulant that prevents blood clots by inhibiting vitamin K–dependent clotting factor synthesis.

Structure of Warfarin

• 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

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