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.
Thesis (M.S.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry