Prodrug forms for the sulfonamide group. IV. Kinetics of hydrolysis of N-sulfonyl pseudourea derivatives.
Two N-sulfonyl pseudourea derivatives, ethyl N-(p-tolylsulfonyl)-1-pyrrolidinecarboximidate and 3-butyl-2-ethyl-1-p-tolylsulfonylpseudourea, were prepared and evaluated as potential prodrug forms for the primary sulfonamide group in the model p-toluenesulfonamide. The stability characteristics of the compounds were examined in aqueous solution at various pH values as well as in the presence of human plasma and rat liver homogenate. The degradation of the derivatives was specific acid and base catalyzed, the maximal stability occurring at pH around 5. The products arising from the degradation included N-ethoxycarbonyl p-toluenesulfonamide, an N-sulfonylurea as well as the parent p-toluenesulfonamide. Human plasma did not significantly catalyze the hydrolysis and although some catalysis was observed in the presence of liver homogenate it is concluded that N-sulfonyl pseudoureas are too stable to be considered as a potentially useful prodrug form for the primary sulfonamide group.
Larsen
J D
JD
Bundgaard
H
H
D006868:Hydrolysis; D007700:Kinetics; D011355:Prodrugs / Q000032:analysis*; D013449:Sulfonamides / Q000032:analysis*; D014105:Tosyl Compounds / Q000032:analysis*; D014508:Urea / Q000031:analogs & derivatives*
D011355:Prodrugs; D013449:Sulfonamides; D014105:Tosyl Compounds; C062155:ethyl N-(4-tolylsulfonyl)-1-pyrrolidinecarboximidate; C062156:3-butyl-2-ethyl-1-(4-tolylsulfonyl)pseudourea; D014508:Urea