Indelicato J M, Pasini C E
Lilly Research Laboratories, Indianapolis, Indiana 46285.
J Med Chem. 1988 Jun;31(6):1227-30. doi: 10.1021/jm00401a026.
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.
通过测量与氢氧根离子的化学反应活性，将一类新型抗菌剂双环吡唑烷酮1的γ-内酰胺环的酰化能力与临床常用抗生素的β-内酰胺环的酰化能力进行了比较。吡唑烷酮的化学反应活性涵盖了经典β-内酰胺抗生素的反应活性范围，其中反应活性最高的1i比所检测的反应活性最高的β-内酰胺头孢他啶的反应活性高13倍。观察到了化学反应活性、微生物活性和3-取代基σp值之间的相关性，并且这种相关性已促使合成了新的、更有效的双环吡唑烷酮。
