Synthesis and biological evaluation of nigranoic acid esters as novel human neutrophil elastase inhibitors

Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as lung disorders and other inflammatory diseases. A series of 12 new nigranoic acid esters were regioselectively synthesised in good yields and evaluated for HNE inhibitory activity. Nigranoic acid exhibited significant inhibitory activity against HNE with the IC₅₀ value of 3.77 μM, and six esters displayed considerable inhibitory effects on HNE with IC₅₀ values in the range of 2.61–8.95 μM. The nigranoic acid esters having phenyls substituted with bromine and trimethoxyls (3h and 3b) showed stronger inhibitory activity on HNE than nigranoic acid.