Potential inhibitors of COPD-relevant serine proteases based on the N-amino-4-imidazolidinone scaffold
Human neutrophil elastase (HNE) and proteinase 3 (PR3) are serine proteases which play a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a multifactorial disorder associated with an imbalance between the levels of COPD-relevant proteases and their physiological protein inhibitors. The N-amino-4-imidazolidinone scaffold was used in the design and synthesis of potential inhibitors of HNE and PR3. The results show that this is a promising avenue of investigation for the development of reversible competitive inhibitors with good selectivity toward HNE and PR3. Molecular docking simulations are supportive of the validity of this approach.