Benzamidoxime prodrugs as antipneumocystic agents

A pharmaceutical formulation comprising, in combination with a pharmaceutically acceptable carrier, a bis-benzamidoxime of Formula II:

• ##STR18## wherein:
• R.sub.1 and R.sub.2 are each independently selected from the group consisting of H, loweralkyl, oxyalkyl, alkoxyalkyl, cycloalkyl, aryl, hydroxyalkyl, aminoalkyl or alkylaminoalkyl;
• R.sub.3 is H, loweralkyl, oxyalkyl, alkoxyalkyl, hydroxyalkyl, cycloalkyl, aryl, aminoalkyl, alkylaminoalkyl or halogen;
• R.sub.4 is --OY, or R.sub.1 and R.sub.4 together represent ##STR19## wherein R.sub.5 is ##STR20## Y is H or loweralkyl;
• n is an integer from 0 to 2;
• and
• A is a heterocyclic aromatic group selected from the group consisting of:
• ##STR21## wherein R.sub.6 and R.sub.7 are each independently selected from the group consisting of H, loweralkyl, halogen, oxyalkyl, oxyaryl, or oxyarylalkyl;
• or a pharmaceutically acceptable salt thereof, wherein said compound is reduced in a mammalian subject after oral administration thereto to produce a benzamidine having anti-Pneumocystis carinii activity.

A bis-benzamidoxime of Formula II:

• ##STR23## wherein:
• R.sub.1 and R.sub.2 are each independently selected from the group consisting of H, loweralkyl, oxyalkyl, alkoxyalkyl, cycloalkyl, aryl, hydroxyalkyl, aminoalkyl or alkylaminoalkyl;
• R.sub.3 is H, loweralkyl, oxyalkyl, alkoxyalkyl, hydroxyalkyl, cycloalkyl, aryl, aminoalkyl, alkylaminoalkyl or halogen;
• R.sub.4 is --OY, or R.sub.1 and R.sub.4 together represent ##STR24## wherein R.sub.5 is ##STR25## Y is H or loweralkyl;
• n is an integer from 0 to 2;
• and
• A is a heterocyclic aromatic group selected from the group consisting of:
• ##STR26## wherein R.sub.6 and R.sub.7 are each independently selected from the group consisting of H, loweralkyl, halogen, oxyalkyl, oxyaryl, or oxyarylalkyl;
• or a pharmaceutically acceptable salt thereof.