Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1368518 | Bioorganic & Medicinal Chemistry Letters | 2016 | 5 Pages |
Abstract
Structure–activity relationship studies of a 1,2,4-triazolo-[3,4-b]thiadiazine scaffold, identified in an HTS campaign for selective STAT3 pathway inhibitors, determined that a pyrazole group and specific aryl substitution on the thiadiazine were necessary for activity. Improvements in potency and metabolic stability were accomplished by the introduction of an α-methyl group on the thiadiazine. Optimized compounds exhibited anti-proliferative activity, reduction of phosphorylated STAT3 levels and effects on STAT3 target genes. These compounds represent a starting point for further drug discovery efforts targeting the STAT3 pathway.
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Related Topics
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Authors
Matthew G. LaPorte, Zhuzhu Wang, Raffaele Colombo, Atefeh Garzan, Vsevolod A. Peshkov, Mary Liang, Paul A. Johnston, Mark E. Schurdak, Malabika Sen, Daniel P. Camarco, Yun Hua, Netanya I. Pollock, John S. Lazo, Jennifer R. Grandis, Peter Wipf,