Exploration of nitrogen heterocycle scaffolds for the development of potent human neutrophil elastase inhibitors.

ABSTRACT: Human neutrophil elastase (HNE) is a potent protease that plays an important physiological role in many processes but is also involved in a variety of pathologies that affect the pulmonary system. Thus, compounds able to inhibit HNE proteolytic activity could represent effective therapeutics. We present here a new series of pyrazolopyridine and pyrrolopyridine derivatives as HNE inhibitors designed as modifications of our previously synthesized indazoles and indoles in order to evaluate effects of the change in position of the nitrogen and/or the insertion of an additional nitrogen in the scaffolds on biological activity and chemical stability. We obtained potent HNE inhibitors with IC₅₀ values in the low nanomolar range (10-50 nM), and some compounds exhibited improved chemical

SUBMITTER: Cantini N 

PROVIDER: S-EPMC8848500 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature