Synthesis and Evaluation of N-Nicotinoyl-2-{2-(2-Methyl-5-Nitroimidazol-1-yl)Ethyloxy}-D,L-Glycine as a Colon-Specific Prodrug of Metronidazole

Metronidazole (MTZ) is a drug of choice for protozoal infections such as luminal amoebiasis. We designed and synthesized N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-D,L-glycine (NMG) as a colon-specific prodrug of MTZ. The synthetic yield of NMG was about 34%. The apparent partition coefficient of MTZ was greatly reduced by the chemical modification. While (bio)chemically stable in the contents of the upper intestine, NMG was...