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Over 30 compounds, including <i>para</i>-, <i>meta</i>-, and <i>ortho</i>-phenylenediboronic acids, <i>ortho</i>-substituted phenylboronic acids, benzenetriboronic acids, di- and triboronated thiophenes, and pyridine derivatives were investigated as potential β-lactamase inhibitors. The highest activity against KPC-type carbapenemases was found for <i>ortho</i>-phenylenediboronic acid <b>3a</b>, which at the concentration of 8/4 mg/L reduced carbapenems’ MICs up to 16/8-fold, respectively. Checkerboard assays revealed strong synergy between carbapenems and <b>3a</b> with the fractional inhibitory concentrations indices of 0.1–0.32. The nitrocefin hydrolysis test and the whole cell assay with <i>E. coli</i> DH5α transformant carrying <i>bla</i>_KPC-3 proved KPC enzyme being its molecular target. <i>para</i>-Phenylenediboronic acids efficiently potentiated carbapenems against KPC-producers and ceftazidime against AmpC-producers, whereas <i>meta</i>-phenylenediboronic acids enhanced only ceftazidime activity against the latter ones. Finally, the statistical analysis confirmed that <i>ortho</i>-phenylenediboronic acids act synergistically with carbapenems significantly stronger than other groups. Since the obtained phenylenediboronic compounds are not toxic to MRC-5 human fibroblasts at the tested concentrations, they can be considered promising scaffolds for the future development of novel KPC/AmpC inhibitors. The complexation of KPC-2 with the most representative isomeric phenylenediboronic acids <b>1a</b>, <b>2a</b>, and <b>3a</b> was modeled by quantum mechanics/molecular mechanics calculations. Compound <b>3a</b> reached the most effective configuration enabling covalent binding to the catalytic Ser70 residue.