WARFARIN SS MEDICINAL CHEMISTRY (PRATHAM).pptx

WARFARIN - ANTICOAGULANT

1. MEDICINAL CHEMISTRY - II DRUG WARFARIN Launch Launch Wilson and Gisvold’s Textbook

2. INJECTABLES ORAL (VIT. K ANTAGONIST) ANTI – COAGULANTS : (LMW HEPARINS) HEPARIN DALTEPARIN ENOXAPARIN NADROPARIN

3. COUMARIN DERIVATIVES - WARFARIN Coumarin ring Phenyl ring IUPAC NAME - 4-hydroxy-3-(3-oxo-1-phenylbutyl) coumarin . 5 Warfarin, a widely used anticoagulant drug, was  discovered in 1939 and 1948 by Karl Link and his student Harold Campbell. It is a 4-hydroxy coumarin derivative.

4. MECHANISM OF ACTION 4

5. Inhibit Vitamin K epoxide reductase Warfarin acts by antagonizing the antihemorrhagic effect of vitamin K. It inhibits synthesis of vitamin K dependent coagulation factors II, VII, IX, and X by inhibiting vitamin K epoxide reductase, preventing vitamin K from being reduced to its active form.

6. Structure-Activity Relationship (SAR) of Warfarin 1.Coumarin Ring (Core Structure): Warfarin is a derivative of 4-hydroxycoumarin. The coumarin ring is crucial for its anticoagulant activity. The 4-hydroxy group is essential for warfarin's interaction with VKOR, making it critical for its anticoagulant properties. 2. Chirality: Warfarin exists as a racemic mixture of two enantiomers: R-warfarin and S-warfarin . S-warfarin is 3-5 times more potent than R-warfarin in inhibiting VKOR. 3. Substitution at Position 3: The substitution at the 3-position of the coumarin ring with a phenyl group linked to a carbonyl group is key to the interaction with VKOR. 4. Hydrophobic Interactions: The phenyl ring at position 3 increases hydrophobic interactions, which may enhance binding to plasma proteins and VKOR. 5. Substitution of Functional Groups: Alterations of the phenyl ring, such as hydroxylation, can reduce the anticoagulant activity. VKOR – Vitamin k epoxide resuctase .

7. USES -

8. SYNTHESIS OF WARFARIN – 8 ACETIC ANHYDRIDE 4-PHENYLBUT-3-EN-2-ONE

9. Thank you BY – BOHARA PRATHAM S. STUDENT AT SCPER,KOPARGAON