抄録
Various methanesulfonic acid derivatives of p, p'-diaminodiphenylsulfone (Da), which are represented as [chemical formula], were synthesized and their hydrolysis rates in vitro were investigated. The two methanesulfonic acid groups were hydrolyzed by steps in consecutive first-order reactions. The first hydrolysis rate was larger than the second rate in any of the derivatives. The electron-donating groups facilitate and the electron-withdrawing groups retard the hydrolysis. When R is HOCH2 (CHOH)4 (promin), phenyl, p-chlorophenyl, or p-nitrophenyl, the hydrolysis rate was pH-dependent and faster in the acidic region. The general acid catalysis by buffer constituents was studied in detail with promin. As a biopharmaceutical indication on the retardation of free Da liberation, kinetic induction period and the rate of accumulation in vitro were evaluated. Result from promin indicated that the liberation of parental Da in vivo is strikingly slow and a large part of therapeutic dose of promin, which is markedly larger than that of parental Da, may possibly be wasted in an ineffective form. The derivatives substituted with Me or Et have fast hydrolysis rate and these may be better in the avaliability of parenteral Da compared to promin.
