Synthesis and antibacterial activity of triazole and isoxazole derivatives of ampicillin

In order to improve the antibacterial activity of ampicillin, new penicillin derivatives having a 1-aryltriazole-4-carboxamide group or a 5-arylisoxazole-3-carboxamide group at the alpha-position of benzylpenicillin or p-hydroxybenzylpenicillin were synthesized. Some compounds in these series were found to possess high activity against Pseudomonas and other Gram-negative bacteria. In addition, structure-activity relationships, especially the effect of the hydrophobic character of the compounds on activity, were investigated.