The present study describes the synthesis, and evaluation of β‐glucuronidase inhibitory potential of metronidazole analogues. Twenty‐four metronidazole‐tethered benzamide triazoles (28‐51) were synthesized using copper‐catalyzed Huisgen alkyne‐azide cycloaddition reaction, and characterized by using different spectroscopic techniques. All of them were identified as new compounds. Compounds 28–51 demonstrated weak to excellent in vitro β‐glucuronidase inhibitory activity with no toxicity against 3T3 mouse fibroblast cell lines. Compound 51 (IC50=12.41 ± 0.58 μM) was found to be the most active β‐glucuronidase inhibitor among the series, with an activity ∼4 times higher than the standard inhibitor, D‐saccharic acid‐1,4‐lactone (IC50=45.75 ± 2.16 μM).

The asymmetric unit of the title compound, C7H11N3O5S, contains two independent mol­ecules with virtually identical conformations. The imidazole rings of both mol­ecules are essentially planar (r.m.s. deviations = 0.0019 and 0.0038 Å), with a dihedral angle 9.25 (19)° between them. The nitro groups are oriented at 4.5 (2) and 6.44 (13)° with respect to the imidazole rings. In the crystal, mol­ecules are linked to form a three-dimensional framework by C—H⋯O and C—H⋯N hydrogen bonds.

Among the reported triazoles, compounds 3-9, 11, and 13 (IC50 = 6.0 ± 0.03 to 19.8 ± 0.28 µM) were found to be several fold more active than the standard drug acarbose (IC50 = 840 ± 1.73 µM). Compound 5 (IC50 = 6.0 ± 0.03 µM) was the most potent AGIs in the series, about 77- fold more active than acarbose. Therefore, dibenzoazepine linked-triazoles described here can serve as leads for further studies as new non-sugar AGIs.