Instability: Tolbutamide is hydrolyzed to paratoluene sulfonamide by acids. Heating of its filtrate with sodium hydroxide solution produces n-butylamine odour.
Glibenclamide
O
Cl N H
O
OO O
S NN HH
5-Chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl] amino]sulfonyl]phenyl]-2-methoxybenzamide Introduction of cyclohexane on the urea nitrogen; Introduction of side chain on the sulfonyl aromatic ring.
Many simple substituents on the sulfonyl aromatic ring are active.
The p-(β-arylcarboxamidoethyl) grouping seen in second generation compounds is consistent with high potency.
Metabolism
Tolbutamide is metabolized in the liver to p-hydroxyl tolbutamide, retaining about 35% of the activity of the parent compound. it is converted very rapidly to the inactive tolbutamide 4-carboxylic acid.
