Nitroimidazole antibacterial compounds and methods of use thereof

Abstract

Methods, compounds and compositions are provided for inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic bacterial infections, such as mycobacterial and clostridium infections, in vivo using bicyclic nitroimidazole compounds of the formula (II): ##STR1## wherein R.sub.1 is hydrogen, halogen, loweralkyl, haloloweralkyl, cycloalkyl, heterocycle, substituted heterocycle and heterocyclicalkyl; X is oxygen, sulfur or NK.sub.2, where R.sub.2 is hydrogen, loweralkyl, aryl, cycloalkyl, heterocycle, substituted heterocycle, heterocyclicalkyl, COR.sub.3 or SO.sub.2 R.sub.4 CONR.sub.4 R.sub.5, where R.sub.4 and R.sub.5 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyaryl, alkoxyalkoxyaryl, alkylheterocycle, and alkoxyheterocycle; n is 1, 2 or 3; Y and Z are independently selected CH.sub.2, CO, CR.sub.4 R.sub.5 or NR.sub.4, where R.sub.4 and R.sub.5 are as defined above; provided that when n is 2 or 3, the compounds of formula II can be additionally substituted as follows: ##STR2## wherein R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyaryl, alkoxyalkoxyaryl, alkylheterocycle, and alkoxyheterocycle; and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis and Clostridium difficile.