Ibuprofen

• Ibuprofen blocks COX enzymes, decreasing prostaglandin synthesis to ease pain and swelling.
• It is an NSAID used for pain, fever, arthritis, and inflammation relief.

Chemical Formula:

• C₁₃H₁₈O₂

Mechanism of Action:

• Reversible COX-1 and COX-2 inhibitor
• Reduces prostaglandin synthesis → ↓ pain, fever, inflammation

Uses:

• Mild to moderate pain
• Fever
• Dysmenorrhea
• Osteoarthritis, rheumatoid arthritis

Side Effects of:

• GI irritation (less than aspirin)
• Nephrotoxicity (dose-related)
• Risk of cardiovascular events (high doses)

SAR of Ibuprofen:

1. Arylpropionic acid core:

   • Required for COX binding and anti-inflammatory activity.

2. Carboxylic acid group:

   • Forms hydrogen bond with arginine in COX active site.

3. Isobutyl side chain:

   • Enhances hydrophobic interactions; increases potency.

4. Chiral center:

   • Only (S)-enantiomer is active as COX inhibitor.

5. Lipophilicity:

   • Improves membrane permeability and GI absorption.

Synthesis of Ibuprofen (Boot Process – Simplified):

1. Isobutylbenzene is acylated → forms phenylacetyl intermediate
2. Hydrolysis to acid, followed by Reformatsky-type reaction
3. Racemic mixture formed → purified for (S)-ibuprofen

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