N,N′-Linked 1,2-benzisothiazol-3(2H)-one 1,1-dioxides: synthesis, biological activity, and derived radicals

Structure based virtual screening for discovery of novel human neutrophil elastase inhibitors

“…The recent efforts to obtain HNE inhibitors have been focused in designing compounds acting via the above mentioned mechanisms; therefore HNE inhibitors are spread over several compound families such as N-benzoylpyrazoles, 9 benzoxazinones, 10 b-lactams, [11][12][13] and more recently 4-oxo-b-lactams, 14,15 pyridones, 16 saccharine derivatives and N,N 0 -connected saccharin, 17 and also 1,2,5-thiadiazolidin-3-one-1,1-dioxides. 18 Moreover, some interesting natural product lead structures have been discovered.…”

Targeting COPD: advances on low‐molecular‐weight inhibitors of human neutrophil elastase

“…The mechanism‐based inhibition concept still remains very attractive due to its potential for reduced toxicity. Advances in mechanism‐based HNE inhibitors were made on saccharine derived inhibitors by Gütschow's group, especially with the first report on N,N ′‐connected saccharins . Groutas's group recently reported a new series of 1,2,5‐thiadiazolidin‐3‐one 1,1 dioxides that showed high selectivity toward HNE .…”

“…More recently, the same group provided the first examples of N , N ′‐connected saccharins, such as 41 and 42 , which proved to be inhibitors of HNE. Nevertheless, only micromolar activities were accomplished so far and further investigation is crucial on this promising unit …”

Unveiling sultam in drug discovery: spotlight on the underexplored scaffold

“…The results showed that two compounds (compounds 21a and 21b ) moderately inhibited HLE with IC 50 values of 14.1 ± 5.9 μM and 23.4 ± 8.0 μM, respectively. 51…”