title: Simple phosphonic inhibitors of human neutrophil elastase.
abstract: Herein, we describe the synthesis and resulting activity of a complex series of α-aminophosphonate diaryl esters as irreversible human neutrophil elastase inhibitors and their selectivity preference for human neutrophil elastase over several other serine proteases such as porcine pancreatic elastase, trypsin, and chymotrypsin. We synthesized and examined the inhibitory potency of several new simple Cbz-protected α-aminoalkylphosphonate diaryl esters that yielded several new HNE inhibitors, where one of the obtained compounds Cbz-Val(P)(OC(6)H(4)-4-COOMe)(2) displayed an apparent second-order inhibition value at 33,015 M(-1) s(-1).
authors.affiliation: Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Sieńczyk
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Winiarski
authors.forename: Paulina
authors.initials: P
authors.lastname: Kasperkiewicz
authors.forename: Mateusz
authors.initials: M
authors.lastname: Psurski
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Józef
authors.initials: J
authors.lastname: Oleksyszyn
mesh_terms: D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008175:Lung Neoplasms / Q000188:drug therapy*; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D063065:Organophosphonates; D019272:Leukocyte Elastase