Furosemide and Loop Diuretics Structure-Activity Relationship (SAR)

Vocabulary flashcards covering the chemical properties, uses, assay, dosage forms, and structure-activity relationships (SAR) of furosemide and loop diuretics based on the lecture notes.

Furosemide Physical Properties

A white crystalline powder, practically insoluble in water and in methylene chloride, soluble in acetone and in dilute solutions of alkali hydroxides, and sparingly soluble in ethanol.

Furosemide Pharmacological Profile

A diuretic chemically related to sulphonamide diuretics, slightly more potent than organomercurial agents, orally effective, with action independent of body acid-base balance alterations.

Furosemide Indications

Used for the treatment of oedema associated with renal disease, nephritic syndrome, cirrhosis of the liver, and congestive heart failure.

Furosemide Assay

Dissolve the sample in dimethylformamide and titrate against $0.1\,\text{M}$ sodium hydroxide using bromothymol blue solution as indicator.

Furosemide Dosage Forms

Furosemide tablets I.P., B.P., Co-amilofruse tablets B.P., and Furosemide injection B.P.

Loop Diuretics Core Chemical Classes

Derivatives classified as either 5-sulphamoyl-2-amino benzoic acid or 5-sulphamoyl-3-amino benzoic acid derivatives.

Loop Diuretic SAR - C-1 Position

The carbonyl group at C-1 provides optimal diuretic activity.

Loop Diuretic SAR - Position 4

Substitution of an activating group (X) in position 4 by Cl, alkoxy, aniline, benzyl, or benzoyl group increases diuretic activity.

Loop Diuretic SAR - Position 5

The presence of a sulphamoyl group in the 5th position is essential for diuretic activity.

Loop Diuretic SAR - 2nd Amino Group Substitution

The presence of furfuryl, phenyl, and thienyl methyl group at the 2nd amino group of 5-sulphamoyl-2-amino benzoic acid gives maximum diuretic activity.

Loop Diuretic SAR - 3rd Amino Group Substitution

A wide range of alkyl groups can be substituted at the 3rd amino group of 5-sulfamoyl-3-amino benzoic acid without modifying optimal diuretic activity.

Loop Diuretic Optimal Pharmacophore Design

A molecule featuring a weakly acidic group to direct the drug to the kidney, an alkylating moiety to react with sulphydryl groups, and lipophilic groups.

Azosemide

A 5-sulphamoyl-2-amino benzoic acid derivative loop diuretic structurally related to furosemide.