کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2481831 1556248 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanism of hydrolysis of a novel indolocarbazole topoisomerase I inhibitor
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Mechanism of hydrolysis of a novel indolocarbazole topoisomerase I inhibitor
چکیده انگلیسی

The degradation kinetics and reaction product profile of the antitumor agent 1 in aqueous solution was studied. Hydrolysis of the pendant imide ring of 1 is the primary mode of thermal degradation in aqueous solution, and the pH rate profile of 1 has a V-shape indicating that hydrolysis of the imide ring can be catalyzed by either acid or base. Hydrolysis of 1 to the anhydride derivative 3 or the dicarboxylic acid derivative 4 is stepwise and the intermediates 2a and 2b formed by initial hydrolytic attack have been observed under alkaline conditions. An overall mechanism for the hydrolysis of 1 in aqueous solution has been proposed. Extrapolating Arrhenius behavior to the hydrolysis reaction of 1 in aqueous solution maintained at a pH value of 4 suggests an aqueous buffered formulation has sufficient thermal stability to be considered a robust room temperature drug product.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 39, Issue 5, 18 March 2010, Pages 291–297
نویسندگان
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