Exploring the functional space of thiiranes as gelatinase inhibitors using click chemistry

A series of 4-[(triazolyl)methoxy]phenyl analogs of the phenoxyphenyl-substituted thiirane SB-3CT 1 was evaluated for its ability to inhibit gelatinases, members of the matrix metalloproteinase family of enzymes. The triazole segment of these inhibitors was assembled using the Meldal-Sharpless coppe...

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Bibliographic Details
Authors: Testero, Sebastian Andres, Llarrull, Leticia Irene, Fisher, Jed F., Chang, Mayland, Mobashery, Shahriar
Format: article
Status:Published version
Publication Date:2011
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/129195
Online Access:http://hdl.handle.net/11336/129195
Access Level:Open access
Keyword:CUAAC CLICK CHEMISTRY
GELATINASE INHIBITOR
MMP
THIIRANE
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Description
Summary:A series of 4-[(triazolyl)methoxy]phenyl analogs of the phenoxyphenyl-substituted thiirane SB-3CT 1 was evaluated for its ability to inhibit gelatinases, members of the matrix metalloproteinase family of enzymes. The triazole segment of these inhibitors was assembled using the Meldal-Sharpless copper-catalyzed Huisgen dipolar cycloaddition of an azide and a terminal alkyne. While these triazole derivatives possessed fair activity as gelatinase inhibitors, an intermediate used in the dipolar cycloaddition, 4-(propargyloxy)phenyl derivative 2, showed very good activity (<50% inhibitory activity following a 3 h pre-incubation of 2 at a concentration of 3 μM) as an inhibitor of human matrix metalloproteinase-2.