Structure
Furosemide Chemical Structure – C12H11ClN2O5S
Structure-Activity Relationship (SAR) of Furosemide
Furosemide is a loop diuretic used primarily for the treatment of edema and hypertension.
Its pharmacological activity is largely due to its ability to inhibit the Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle in the kidneys.
The SAR of furosemide involves:
1. Sulfamoyl Anthranilic Acid Derivative:
The core structure is based on sulfamoyl anthranilic acid, which is critical for its diuretic activity. This group is essential for binding to the chloride site of the transporter.
2. Furanyl Moiety:
The furanyl group attached to the amino group of the anthranilic acid contributes significantly to the diuretic potency of the drug.
3. Phenoxyacetic Acid Derivative:
The attachment of a phenoxyacetic acid moiety increases the drug's potency and bioavailability.
4. Acidic Nature:
The acidic nature of furosemide enhances its solubility and excretion, which is important for its diuretic action.
Synthesis of Furosemide
The synthesis of Furosemide generally involves the following key steps:
1. Condensation Reaction:
4−Chloro−5−sulfamoylanthranilicacid + Phenoxyaceticacid → Intermediate
The condensation of 4-chloro-5-sulfamoylanthranilic acid with phenoxyacetic acid yields an intermediate compound.
2. Cyclization to Form Furosemide:
Intermediate → Furosemide
The intermediate then undergoes a cyclization process, often involving a reaction with a furfurylamine, to form furosemide.
This synthesis pathway highlights the combination of the sulfamoyl anthranilic acid core with the furanyl and phenoxyacetic acid components, crucial for the drug's diuretic activity. The specific conditions and reagents for these reactions can vary, and additional steps may be involved in the process, especially for purification and yield optimization in industrial settings.
Mode of action
It produces a diuretic effect by competitively inhibiting sodium-potassium-chloride cotransporters in the nephron and blocking the transport of sodium ions during reabsorption.
Due to this inhibition, more water, sodium, chloride, magnesium, calcium, hydrogen, and potassium ions are excreted.
Uses
It is used as loop diuretics
It treats edema (tissue fluid overload).
Used in hypertension.