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ID: ALA1136470

Journal: Bioorg Med Chem Lett

Title: Rational design, synthesis and structure-activity relationships of a cyclic succinate series of TNF-alpha converting enzyme inhibitors. Part 1: lead identification.

Authors: Xue CB, He X, Roderick J, Corbett RL, Duan JJ, Liu RQ, Covington MB, Newton RC, Trzaskos JM, Magolda RL, Wexler RR, Decicco CP.

Abstract: Rational design based on the broad spectrum MMP inhibitor CGS 27023A led to the identification of a novel series of cyclic succinate TACE inhibitors. As a mixture of two enantiomers, the lead compound 17b exhibited potent enzyme activity (IC(50)=8 nM) in the inhibition of porcine TNF-alpha converting enzyme (pTACE) and excellent selectivity over aggrecanase and MMP-1, -2 and -9.

CiteXplore: 14643312

DOI: 10.1016/j.bmcl.2003.09.056