Larsen J D, Bundgaard H
Acta Pharm Nord. 1989;1(1):31-40.
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.
制备了两种N-磺酰基pseudourea衍生物，即N-(对甲苯磺酰基)-1-吡咯烷甲脒乙酯和3-丁基-2-乙基-1-对甲苯磺酰基pseudourea，并将其作为模型对甲苯磺酰胺中伯磺酰胺基团的潜在前药形式进行了评估。在不同pH值的水溶液以及人血浆和大鼠肝脏匀浆存在的情况下，研究了这些化合物的稳定性特征。衍生物的降解是由特定的酸和碱催化的，最大稳定性出现在pH约为5时。降解产生的产物包括N-乙氧羰基对甲苯磺酰胺、一种N-磺酰脲以及母体对甲苯磺酰胺。人血浆没有显著催化水解，尽管在肝脏匀浆存在的情况下观察到了一些催化作用，但得出的结论是，N-磺酰基pseudoureas过于稳定，不能被视为伯磺酰胺基团潜在有用的前药形式。
