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<i>Acinetobacter baumannii</i> is a Gram-negative organism listed as an urgent threat pathogen by the World Health Organization (WHO). Carbapenem-resistant <i>A. baumannii</i> (CRAB), especially, present therapeutic challenges due to complex mechanisms of resistance to <i>β</i>-lactams. One of the most important mechanisms is the production of <i>β</i>-lactamase enzymes capable of hydrolyzing <i>β</i>-lactam antibiotics. Co-expression of multiple classes of <i>β</i>-lactamases is present in CRAB; therefore, the design and synthesis of “cross-class” inhibitors is an important strategy to preserve the efficacy of currently available antibiotics. To identify new, nonclassical <i>β</i>-lactamase inhibitors, we previously identified a sulfonamidomethaneboronic acid <b>CR167</b> active against <i>Acinetobacter</i>-derived class C <i>β</i>-lactamases (ADC-7). The compound demonstrated affinity for ADC-7 with a <i>K</i>_i = 160 nM and proved to be able to decrease MIC values of ceftazidime and cefotaxime in different bacterial strains. Herein, we describe the activity of <b>CR167</b> against other <i>β</i>-lactamases in <i>A. baumannii</i>: the cefepime-hydrolysing class C extended-spectrum <i>β</i>-lactamase (ESAC) ADC-33 and the carbapenem-hydrolyzing OXA-24/40 (class D). These investigations demonstrate <b>CR167</b> as a valuable cross-class (C and D) inhibitor, and the paper describes our attempts to further improve its activity. Five chiral analogues of <b>CR167</b> were rationally designed and synthesized. The structures of OXA-24/40 and ADC-33 in complex with <b>CR167</b> and select chiral analogues were obtained. The structure activity relationships (SARs) are highlighted, offering insights into the main determinants for cross-class C/D inhibitors and impetus for novel drug design.