Structure of Acetazolamide
Acetazolamide is a sulfonamide derivative with a central sulfonamide group attached to a benzene ring and a dithiocarbamate moiety.
Chemical Formula: C₄H₆N₂O₃S₂
Structure of Acetazolamide
Mode of Action
Carbonic Anhydrase Inhibition: Acetazolamide inhibits the enzyme carbonic anhydrase, which is pivotal in the reversible hydration of carbon dioxide.
Renal Effects: In the proximal tubules of the kidneys, this inhibition leads to decreased reabsorption of bicarbonate, resulting in increased excretion of bicarbonate, sodium, potassium, and water.
Metabolic Acidosis: Causes a mild metabolic acidosis by reducing bicarbonate levels in the blood.
Uses
Glaucoma: Reduces intraocular pressure by decreasing aqueous humor production.
Epilepsy: Used as an adjunctive therapy in certain types of seizures.
Altitude Sickness: Prevents and treats acute mountain sickness by inducing diuresis and metabolic acidosis.
Metabolic Alkalosis: Corrects metabolic alkalosis by promoting bicarbonate excretion.
Diuretic: Employed in cases where other diuretics are ineffective.
Structure-Activity Relationship (SAR)
Sulfonamide Group: Essential for binding to the active site of carbonic anhydrase.
Dithiocarbamate Moiety: Enhances binding affinity and specificity for the enzyme.
Benzene Ring: Provides structural stability and facilitates proper orientation for enzyme interaction.
Substituents: Electron-withdrawing groups on the benzene ring can increase inhibitory potency by enhancing binding interactions.
Synthesis
Acetazolamide is synthesized through the reaction of sulfanilamide with carbon disulfide and subsequent cyclization.
Synthetic Route:
Starting Material: Sulfanilamide.
Reaction with Carbon Disulfide: Forms a dithiocarbamate intermediate.
Cyclization: Intramolecular reaction to form the acetazolamide structure.
Purification: Isolation and recrystallization to obtain pure acetazolamide.
Reaction Scheme:
Sulfanilamide + CS₂ → Dithiocarbamate Intermediate → Acetazolamide