Synthesis and SAR of novel benzoxaboroles as a new class of β-lactamase inhibitors

A new class of benzoxaborole β-lactamase inhibitors were designed and synthesized. 6-Aryloxy benzoxaborole 22 inhibited AmpC P99 and CMY-2 with Ki values in the low nanomolar range. Compound 22 restored antibacterial activity of ceftazidime against Enterobacter cloacae P99 expressing AmpC, a class C β-lactamase enzyme. The SAR around the arylbenzoxaboroles, which included the influence of linker and substitutions was also established.

Graphical abstractA new class of benzoxaborole β-lactamase inhibitors is described. 6-Aryloxy benzoxaborole, 22, inhibited AmpC P99 and CMY-2 with Ki values in the low nanomolar range. Compound 22 restored antibacterial activity of ceftazidime against Enterobacter cloacae P99 expressing AmpC.Figure optionsDownload full-size imageDownload as PowerPoint slide