Prodrugs - Part 2. Acylbenzoate esters of metronidazole

The design and synthesis of a series of chain and cyclic acylbenzoate esters of metronidazole are described. The esters are designed to be both lipophilic and reactive in their hydrolysis reactions. The alkaline hydrolyses of the chain 2-acylbenzoates are relatively rapid, employing an intramolecular catalytic route, while the reactions of the 4-formylbenzoate and cyclic 2-formylbenzoate are also relatively rapid using the normal pathway. The anti-bacterial activity of the esters are comparable to that of metronidazole.