Rational design, synthesis and structure–activity relationships of a cyclic succinate series of TNF-α converting enzyme inhibitors. Part 2: lead optimization

…, M Qian, MD Ribadeneira, K Vaddi, DD Christ…

Index: Xue, Chu-Biao; He, Xiaohua; Roderick, John; Corbett, Ronald L.; Duan, James J.-W.; Liu, Rui-Qin; Covington, Maryanne B.; Qian, Mingxin; Ribadeneira, Maria D.; Vaddi, Krishna; Christ, David D.; Newton, Robert C.; Trzaskos, James M.; Magolda, Ronald L.; Wexler, Ruth R.; Decicco, Carl P. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 24 p. 4299 - 4304

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Citation Number: 35

Abstract

Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-{[4-(4-quinolinyloxymethyl) anilinyl] carbonyl}-1-cyclohexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-α release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S, 6S)-1-methyl-6-{[4-(2-methyl-4-quinolinylmethoxy ...