The acylating potential of gamma-lactam antibacterials: base hydrolysis of bicyclic pyrazolidinones.
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.
Indelicato
J M
JM
Lilly Research Laboratories, Indianapolis, Indiana 46285.
Pasini
C E
CE
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D007769:Lactams; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007769:Lactams