Inhibition of serine proteases by a new class of cyclosulfamide-based carbamylating agents.
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.
Yang
Qingliang
Q
Department of Chemistry, Wichita State University, 1845 N Fairmount Avenue, Wichita, KS 67260, USA.
Li
Yi
Y
Dou
Dengfeng
D
Gan
Xiangdong
X
Mohan
Swathi
S
Groutas
Christopher S
CS
Stevenson
Laura E
LE
Lai
Zhong
Z
Alliston
Kevin R
KR
Zhong
Jiaying
J
Williams
Todd D
TD
Groutas
William C
WC
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
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase