J. D. Larsen, H. Bundgaard, V. H. Lee
Nov 1, 1988
Citations
1
Influential Citations
16
Citations
Journal
International Journal of Pharmaceutics
Abstract
Abstract Various N -acyl derivatives (acetyl, benzoyl, N , N -diethylaminoacetyl and morpholinoacetyl) of the model sulfonamide N -methyl- p -toluenesulfonamide were synthesized and evaluated as potential prodrug forms for the sulfonamide group occurring in e.g. carbonic] anhydrase inhibitors. The kinetics of hydrolysis of the derivatives were determined at 37°C in the pH range 0–12 and in the presence of human plasma. Maximal stability was achieved at pH around 4. The N -acyl compounds were readily hydrolyzed enzymatically to yield the parent sulfonamide in quantitative amounts. The derivatives with an ionizable amino function in the acyl moiety possess a high water-solubility as well as adequate lipophilicity at physiological pH. Since various N -methylsulfonamides are known to undergo demethylation in vivo a promising prodrug approach for a primary sulfonamide may be N -acylation of the corresponding N -methylsulfonamide.