Synthesis and structure–activity relationship of a novel, achiral series of TNF-α converting enzyme inhibitors

…, M Qian, MD Ribadeneria, K Vaddi, JM Trzaskos…

Index: Gilmore, John L.; King, Bryan W.; Harris, Cathy; Maduskuie, Thomas; Mercer, Stephen E.; Liu, Rui-Qin; Covington, Maryanne B.; Qian, Mingxin; Ribadeneria, Maria D.; Vaddi, Krishna; Trzaskos, James M.; Newton, Robert C.; Decicco, Carl P.; Duan, James J.-W. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 10 p. 2699 - 2704

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Citation Number: 32

Abstract

A novel series of achiral TNF-α converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11nM in a porcine TACE assay and inhibited TNF-α production in an LPS-stimulated whole blood assay with an IC50 value of 23nM for the most potent one. They also have excellent selectivities over related metalloproteases including aggrecanases.