Utilization of the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide scaffold in the design of potential inhibitors of human neutrophil proteinase 3.
The S' subsites of human neutrophil proteinase 3 (Pr 3) were probed by constructing diverse libraries of compounds based on the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide using combinational and click chemistry methods. The multiple points of diversity embodied in the heterocyclic scaffold render it well-suited to the exploration of the S' subsites of Pr 3. Molecular modeling studies suggest that further exploration of the S' subsites of Pr 3 using the aforementioned heterocyclic scaffold may lead to the identification of highly selective, reversible competitive inhibitors of Pr 3.
Dou
Dengfeng
D
Department of Chemistry, Wichita State University, Wichita, KS 67260, United States.
He
Guijia
G
Li
Yi
Y
Lai
Zhong
Z
Wei
Liuqing
L
Alliston
Kevin R
KR
Lushington
Gerald H
GH
Eichhorn
David M
DM
Groutas
William C
WC
D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D053146:Myeloblastin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
C549117:1,2,3,5-thiatriazolidin-3-one 1,1-dioxide; D015842:Serine Proteinase Inhibitors; D014230:Triazoles; D053146:Myeloblastin