cps-49 and 2-4-difluoroaniline

A stability-indicating high-performance liquid chromatography method to quantify 2-(2,4-difluorophenyl)-4,5,6,7-tetrafluoroisoindoline-1,3-dione (NSC-726796) and its three main degradation products was developed. This method was used to investigate its degradation kinetics and mechanism. The reaction follows first-order kinetics and appears to be base catalyzed with the maximum stability at pH 1. The products were identified as 2-(2,4-difluorophenylcarbamoyl)-3,4,5,6-tetrafluorobenzoic acid (NSC-749820), 2,4-difluoroaniline, and tetrafluorophthalic acid. The parent drug, NSC-726796, was also found to react with methanol and ethanol. NSC-726796 demonstrates antiangiogenic activity, however, when its degradant NSC749820 does not show antiangiogenic activity.

Topics: Angiogenesis Inhibitors; Aniline Compounds; Animals; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Stability; Ethanol; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Methanol; Neovascularization, Physiologic; Phthalic Acids; Phthalimides; Rats; Reproducibility of Results; Solvents; Technology, Pharmaceutical; Temperature; Tissue Culture Techniques