Previously, we have shown that 3’,4’-difluoroquercetin (di-F-Q) serve as dual inhibitors against broad-spectrum β-lactamases as well as the efflux pumps. The dual inhibitors effectively potentiated aztreonam (ATM) against various clinical strains of carbapenemase-resistant Pseudomonas aeruginosa (CRPA). While most antimicrobial agents active against Gram negatives tend to show high polarity and charges, the di-F-Q derivatives are nonpolar. Therefore, we reasoned that their ATM-potentiating activity could be enhanced through introduction of a polar substituent. In this study, we prepared a series of the di-F-Q derivatives substituted with easily ionizable polar moieties at the 7-O positions. The newly synthesized compounds were then screened for their inhibitory activity against various β-lactamases and efflux pumps. Two compounds with inhibitory activity against ATM-hydrolyzing β-lactamases (NDM-1 and OXA-10) and efflux pumps were chosen, and in vitro and in vivo evaluation of their ATM-potentiating activity was performed, which led to identification of a new ATM-potentiating agent against various clinical CRPAs.