Our research aim was to design, synthesize, and study the competitive enzyme inhibition kinetics of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives as potential non-²-lactam ²-lactamase inhibitors. All compounds (1-13) passed the Lipinski’s rule of 5 test and were docked into the active site of TEM-1 ²-lactamase. PBD derivatives 1-7 were synthesized in high yields and tested for their potency against TEM-1 and P99 ²-lactamases. Kinetic data showed that compounds 1, 4, 5, and 7 possessed inhibitory activity against TEM-1 ranging from 4-34 %. Docking results revealed significant interactive spanning of the active site of TEM-1 by PBDs. The limited inhibitory activity of the compounds, 1-7 could be attributed to the lack of solubility and bulky nature of the molecules, thus limiting the optimal ligand-enzyme interactions. 1,2,4- Oxadiazolinones (8-13) were further synthesized to reduce the steric hindrance of the PBD scaffolds while promoting the electrophilicity of the potentially active lactam and also evaluated for potency.