Rapid hydrolysis of amides under physiological conditions: Influence of the microenvironment on the stability of the amide bond

A new class of bicyclic carboxyamides 1a-9a differing with respect to substitution patterns and exoendo geometry has been synthesized. These amides are characterized by a structure-dependent unusual rapid hydrolysis rate at physiological conditions. The corresponding bicyclic anhydrides might be used as tools for masking and modifiying therapeutic agents containing amine functionalities.