Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 23, Pages 7614-7624Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm801063n
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Funding
- National Health and Medical Research Council of Australia
- Incitive Limited (Australia)
- Auckland Division of the Cancer Society of New Zealand
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Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure-activity relationships around the core bicyclic thioxofuropyridinone and pendant furan ring. This resulted in the identification of a submicromolar inhibitor of the perforin-induced lysis of Jurkat T-lymphoma cells.
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