Structure of Furosemide
Furosemide is a sulfonamide derivative belonging to the loop diuretic class, characterized by a benzothiazine structure with a furan ring and a sulfonamide group.
Chemical Formula: C₁₅H₁₉ClN₂O₅S₂
Mode of Action
Loop of Henle Inhibition: Inhibits the Na⁺/K⁺/2Cl⁻ symporter in the ascending limb of the loop of Henle.
Sodium, Potassium, Chloride Excretion: Promotes excretion of these ions, leading to significant diuresis.
Calcium and Magnesium Retention: Increases the reabsorption of calcium and magnesium, reducing the risk of kidney stones.
Uses
Edema: Effective in managing edema associated with congestive heart failure, liver cirrhosis, and renal disease.
Hypertension: Used to lower blood pressure by reducing blood volume.
Hypercalcemia: Treats elevated calcium levels by promoting its excretion.
Acute Pulmonary Edema: Provides rapid diuresis to alleviate fluid accumulation in the lungs.
Hyponatremia: Manages low sodium levels by promoting sodium excretion
Structure-Activity Relationship (SAR)
Benzothiazine Core: Essential for loop diuretic activity by targeting the Na⁺/K⁺/2Cl⁻ symporter.
Furan Ring: Enhances binding affinity and potency by facilitating proper orientation for transporter inhibition.
Sulfonamide Groups: Critical for interaction with the transporter; substitutions can affect potency and duration of action.
Chlorine Substituent: Increases lipophilicity, enhancing membrane permeability and bioavailability.
Synthesis
Furosemide is synthesized through the condensation of sulfamoyl chloride with appropriate aromatic compounds, followed by cyclization to form the benzothiazine core.
Synthetic Route:
Starting Material: Sulfamoyl chloride.
Condensation Reaction: React with a substituted aromatic compound containing a furan ring.
Cyclization: Formation of the benzothiazine ring structure.
Purification: Isolation and recrystallization to obtain pure furosemide.
· Reaction Scheme:
Sulfamoyl Chloride + Substituted Aromatic Compound → Furosemide