The acylating potential of .gamma.-lactam antibacterials: base hydrolysis of bicyclic pyrazolidinones

Journal of Medicinal Chemistry
1988.0

Abstract

The acylating ability of the gamma-lactam ring of a new class of antibacterial agent, the bicyclic pyrazolidinones 1, was compared to that of the beta-lactam ring of clinically useful antibiotics by measuring chemical reactivity with hydroxide ion. The pyrazolidinone chemical reactivity spans the reactivity of classical beta-lactam antibiotics and the most reactive, 1i, is 13 times more reactive than the most reactive beta-lactam examined, ceftazidime. A correlation involving chemical reactivity, microbiological activity, and 3-substituent sigma p values was observed, and the correlation has led to the synthesis of new more potent bicyclic pyrazolidinones.

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