Hashimoto N, Hirano K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Sagisu, Fukushima-ku, Osaka 553, Japan.
J Pharm Sci. 1998 Sep;87(9):1091-6. doi: 10.1021/js980048z.
The isomerization reactions of ceftibuten and ceftibuten-related compounds in aqueous solution were investigated to estimate the substitution effect on the isomerization reaction and identify the three proximal dissociation constants of ceftibuten kinetically from the pH-rate profiles. The isomerization reaction of ceftibuten-related compounds was influenced by the substituents near the double bond at the C7-side chain, and the electron-withdrawing substituent was found to increase the isomerization rate. Ceftibuten isomerized at the C7-side chain, and the isomerization rate was influenced by the dissociation of the C7-side chain carboxylic acid and aminothiazole in the acidic pH region. The dissociation constants of ceftibuten were assigned by comparing the isomerization rates of ceftibuten with its related compounds at various pH conditions, and the pKas 2.3, 3.2, and 4.5 were attributed to the 4-carboxylic acid, 7-carboxylic acid, and 7-aminothiazole, respectively.
研究了头孢布烯及其相关化合物在水溶液中的异构化反应，以评估取代基对异构化反应的影响，并从pH-速率曲线中动力学确定头孢布烯的三个近端解离常数。头孢布烯相关化合物的异构化反应受C7侧链双键附近取代基的影响，发现吸电子取代基会提高异构化速率。头孢布烯在C7侧链发生异构化，异构化速率受酸性pH区域中C7侧链羧酸和氨基噻唑解离的影响。通过比较头孢布烯及其相关化合物在不同pH条件下的异构化速率来确定头孢布烯的解离常数，pKa 2.3、3.2和4.5分别归因于4-羧酸、7-羧酸和7-氨基噻唑。
