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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492831 | PMC |
| http://dx.doi.org/10.1016/j.abb.2008.04.020 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Potent inhibition of Norwalk virus by cyclic sulfamide derivatives.
Bioorg Med Chem
October 2011
Department of Chemistry, Wichita State University, Wichita, KS 67260, United States.
A new class of compounds that exhibit anti-norovirus activity in a cell-based system and embody in their structure a cyclosulfamide scaffold has been identified. The structure of the initial hit (compound 2a, ED(50) 4 μM, TD(50) 50 μM) has been prospected by exploiting multiple points of diversity and generating appropriate structure-activity relationships.
View Article and Find Full Text PDFDesign and synthesis of inhibitors of noroviruses by scaffold hopping.
Bioorg Med Chem
October 2011
Department of Chemistry, Wichita State University, Wichita, KS 67260, United States.
A scaffold hopping strategy was employed to identify new chemotypes that inhibit noroviruses. The replacement of the cyclosulfamide scaffold by an array of heterocyclic scaffolds lead to the identification of additional series of compounds that possessed anti-norovirus activity in a cell-based replicon system.
View Article and Find Full Text PDFInhibition of serine proteases by a new class of cyclosulfamide-based carbamylating agents.
Arch Biochem Biophys
July 2008
Department of Chemistry, Wichita State University, 1845 N Fairmount Avenue, Wichita, KS 67260, USA.
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.
View Article and Find Full Text PDFDesign, synthesis, and in vitro evaluation of inhibitors of human leukocyte elastase based on a functionalized cyclic sulfamide scaffold.
Bioorg Med Chem
February 2004
Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
The design of novel functionalized templates capable of binding to the active site of serine proteases could potentially lead to the development of potent and highly selective non-covalent inhibitors of these enzymes. Using the elastase-turkey ovomucoid inhibitor complex and insights gained from earlier work based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I), a surrogate cyclosulfamide scaffold (II) was used for the first time in the design of reversible inhibitors of human leukocyte elastase. Compounds 7 and 8 were found to be micromolar reversible inhibitors of the enzyme.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!