Nitroimidazole antibacterial compounds and methods of use thereof

A compound of the formula:

• ##STR45## wherein R.sub.1 is selected from the group consisting of hydrogen, halogen, loweralkyl, haloloweralkyl, cycloalkyl, heterocycle, substituted heterocycle and heterocyclicalkyl;
• and R.sub.4 is selected from the group consisting of hydrogen, loweralkyl, haloloweralkyl, aryl, alkylaryl, alkoxy, alkoxyalkyl, alkoxyaryl, haloalkoxyaryl, alkoxyalkoxyaryl, carbamate, carboxamide, alkylheterocycle, and alkoxyheterocycle;
• n is 1, 2 or 3;
• and the pharmaceutically acceptable salts thereof.

A method of inhibiting the growth of pathogenic bacterium comprising contacting the bacterium with a growth inhibitory amount of a bicyclic nitroimidazole compound of the formula:

• ##STR46## wherein R.sub.1 is hydrogen, halogen, loweralkyl, haloloweralkyl, cycloalkyl, heterocycle, substituted heterocycle and heterocyclicalkyl;
• R.sub.4 and R.sub.5 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxy, alkoxyalkyl, alkoxyaryl, alkoxyalkoxyaryl, carbamate, carboxamide, alkylheterocycle, and alkoxyheterocycle;
• and
• n is 1, 2 or 3;
• provided that when n is 2 or 3, the compounds can be additionally substituted as follows:
• ##STR47## wherein R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from hydrogen, loweralkyl, alkylaryl, alkoxyalkyl, alkoxyalkylaryl, alkoxyalkylheterocycle, alkylarylalkylaryl, alkylarylaryl, alkylcycloalkyl, alkoxyaryl, alkylheterocycle, and alkoxyheterocycle;
• and the pharmaceutically acceptable salts thereof.

A method of treating a human or animal subject suffering from an infection by pathogenic mycobacteria or clostridium comprising administering to the subject a therapeutically effective amount of a bicyclic nitroimidazole compound of the formula:

• ##STR49## wherein R.sub.1 is hydrogen, halogen, loweralkyl, haloloweralkyl, cycloalkyl, heterocycle, substituted heterocycle and heterocyclicalkyl;
• and R.sub.4 and R.sub.5 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxy, alkoxyalkyl, alkoxyalkyl, alkoxyalkoxyaryl, carbamate, carboxamide, alkylheterocycle, and alkoxyheterocycle;
• and
• n is 1, 2 or 3;
• provided that when n is 2 or 3, the compounds of formula II can be additionally substituted as follows:
• ##STR50## wherein R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from hydrogen, loweralkyl, aryl, alkylaryl, alkoxyalkyl, alkoxyalkylaryl, alkoxyalkylheterocycle, alkylarylalkylaryl, alkylarylaryl, alkylcycloalkyl, alkoxyaryl, alkylheterocycle, and alkoxyheterocycle;
• and the pharmaceutically acceptable salts thereof;
• alone or together with a pharmaceutically acceptable carrier.