title: Inhibition of serine proteases by a new class of cyclosulfamide-based carbamylating agents.
abstract: A new class of carbamylating agents based on the cyclosulfamide scaffold is reported. These compounds were found to be efficient time-dependent inhibitors of human neutrophil elastase (HNE). Exploitation of the three sites of diversity present in the cyclosulfamide scaffold yielded compounds which inhibited HNE but not proteinase 3 (PR 3) or bovine trypsin. The findings reported herein suggest that the introduction of appropriate recognition elements into the cyclosulfamide scaffold may lead to highly selective agents of potential value in the design of activity-based probes suitable for investigating proteases associated with the pathogenesis of chronic obstructive pulmonary disease.
authors.affiliation: Department of Chemistry, Wichita State University, 1845 N Fairmount Avenue, Wichita, KS 67260, USA.
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Dou
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gan
authors.forename: Swathi
authors.initials: S
authors.lastname: Mohan
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Groutas
authors.forename: Laura E
authors.initials: LE
authors.lastname: Stevenson
authors.forename: Zhong
authors.initials: Z
authors.lastname: Lai
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Alliston
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhong
authors.forename: Todd D
authors.initials: TD
authors.lastname: Williams
authors.forename: William C
authors.initials: WC
authors.lastname: Groutas
mesh_terms: D003500:Cyclization; D015195:Drug Design; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase