252919-38-3Relevant academic research and scientific papers
Rational design, synthesis and structure-activity relationships of a cyclic succinate series of TNF-α converting enzyme inhibitors. Part 2: Lead optimization
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.
, p. 4299 - 4304 (2003)
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)anilinyl] carbonyl}-5-piperidinecarboxamide] exhibited an IC50 value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs.
