Synthesis and Preliminary Biological Evaluation of 3'-Substituted Cephem Sulfones as Potential β-Lactamase Inhibitors

التفاصيل البيبلوغرافية
العنوان:	Synthesis and Preliminary Biological Evaluation of 3'-Substituted Cephem Sulfones as Potential β-Lactamase Inhibitors
المؤلفون:	De Angelis, Francesco, Attorrese, Giuseppe, Cavicchio, Giancarlo, Ciampa, Sabatino, Di Tullio, Alessandra, Fattori, Daniela, Nicoletti, Rosario, Domenici, Enrico
المصدر:	European Journal of Organic Chemistry; August 2001, Vol. 2001 Issue: 16 p3075-3081, 7p
مستخلص:	3'-Substituted cephem sulfones, as well as the unsubstituted congener, were synthesized and biologically evaluated as β-lactamase inhibitors. Sodium 3'-substituted cephalosporanate sulfones 4 and 5 were prepared starting from 7-aminodeacetoxycephalosporanic acid (7-ADCA, 6) by a bromodeamination reaction, followed by reduction of the 7-halo derivative. Selective, radical bromination at C-3' on the Δ³-isomer, followed by nucleophilic substitution and then retroisomerization at Δ², afforded the required derivatives. 3'-Unsubstituted and 3'-acetoxycephem sulfones 2 and 3 were prepared using routine chemistry. The 3'-substituted cephem sulfone derivatives, evaluated as β-lactamase inhibitors by IC50 determinations, behave as weak inhibitors of the class D oxacillinase OXA1 from Escherichia coli and the class C β-lactamase of Enterobacter cloacae P99. Conversely, the 3'-unsubstituted cephem sulfone 2 was shown to be comparable to sulbactam and even more active than clavulanic acid against the latter enzyme. The activity of 2 against E. cloacae P99 was also greatly enhanced by prolonging the pre-incubation time. Considerations as to the mechanism of inhibition are also put forward.
قاعدة البيانات:	Supplemental Index

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تدمد:	1434193X 10990690
DOI:	10.1002/1099-0690(200108)2001:16<3075::AID-EJOC3075>3.0.CO;2-A