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Updated: Jul 18, 2026

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Beta-aminoketones as prodrugs with pH-controlled activation
Ana Luísa Simplício1, John M Clancy, John F Gilmer
1School of Pharmacy, Trinity College, Dublin 2, Ireland. anas@itqb.unl.pt
Abstract:
N-Mannich bases have been widely applied as prodrugs of amine drugs. The analogous C-Mannich bases (beta-aminoketones) have received rather less attention probably because they are not sufficiently susceptible to elimination at pHs encountered in vivo. Compounds in which there is a thermodynamic advantage to elimination may be an exception. In this study, the physicochemical characteristics of a series of Michael amino addition adducts of chalcone and other carbonyl compounds is explored. The ketone adducts rapidly eliminate at around pH 7.4 (t(1/2) < 15 min) releasing the amine and the ketone but they are stable under acidic conditions. The Michael adducts are more lipophilic than the parent amines and have significantly suppressed ionisation characteristics at biologically relevant pH values.
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