Medicinal Chemistry (Kidney Drugs)

Which functional group is essential for carbonic anhydrase inhibitory activity in acetazolamide?

• Carboxylic acid

• Sulfonamide (-SO₂NH₂)

• Phenol

• Amide

In loop diuretics like furosemide, what structural feature allows binding to the Na⁺/K⁺/2Cl⁻ cotransporter?

• Guanidine group

• Ether linkage

• Sulfonamide or carboxylic acid group

• Ester group

What is the purpose of the 6-chloro substituent on the thiazide ring system?

• Improves oral bioavailability

• Enhances aqueous solubility

• Increases diuretic activity through electron withdrawal

• Reduces diuretic potency

The replacement of an O-glucoside linkage with a C-glucoside in SGLT2 inhibitors improves what property?

• Renal clearance

• Half-life and metabolic stability

• Water solubility

• Selectivity for SGLT1

Which SAR feature of finerenone enhances selectivity toward mineralocorticoid receptor (MR)?

• Methyl at position 2

• 3-carboxamide group

• Para-hydroxy substitution

• Bulky alkyl side chain

The 1,4-dihydro-1,6-naphthyridine core in finerenone is designed to:

• Mimic aldosterone’s steroid nucleus

• Enhance lipophilicity for BBB penetration

• Fit tightly into the MR ligand-binding pocket

• Improve glucose reabsorption

The SAR of amiloride indicates the guanidine group is critical for:

• Crossing the blood-brain barrier

• Na⁺ channel pore interaction

• Metabolic stability

• SGLT2 selectivity

Which structural element in empagliflozin enhances its SGLT2 potency and selectivity?

• Chlorine atom on glucose

• Tetrahydrofuran linker

• Methyl substitution at C-2

• Ether linkage between aryl rings

Why do early O-aryl glucosides like phlorizin have poor oral bioavailability?

• They are too hydrophilic

• Prone to enzymatic cleavage by β-glucosidases

• Bind weakly to SGLT2

• Undergo extensive renal metabolism

Which thiazide SAR feature is essential for IV formulation development?

• Aromaticity

• Free carboxylic acid

• Multiple acidic protons for sodium salt formation

• Fluorine substitution at C-4