Towards an efficient prodrug of the alkylating metabolite monomethyltriazene: synthesis and stability of N-acylamino acid derivatives of triazenes.
نویسندگان
چکیده
A series of 3-[alpha-(acylamino)acyl]-1-aryl-3-methyltriazenes 6a-l, potential cytotoxic triazene prodrugs, were synthesised by coupling 1-aryl-3-methyltriazenes to N-acylamino acids. Their hydrolysis was studied in isotonic pH 7.4 phosphate buffer and in human plasma, while hydrolysis of the derivative 6a was studied in more depth across a range of pH values. Prodrugs 6a-l hydrolyse by cleavage of the triazene acyl group to afford the corresponding monomethyltriazenes. Studies in human plasma demonstrate that acylation of the alpha-amino group of the amino acid carrier is an effective means of reducing the chemical reactivity of the alpha-aminoacyl derivatives while retaining a rapid rate of enzymatic hydrolysis. These derivatives displayed logP values that suggest they should be well absorbed through biological membranes.
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ورودعنوان ژورنال:
- European journal of medicinal chemistry
دوره 44 3 شماره
صفحات -
تاریخ انتشار 2009