441773-75-7Relevant articles and documents
Synthesis and structure-activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors
Xue, Chu-Biao,Chen, Xiao-Tao,He, Xiaohua,Roderick, John,Corbett, Ronald L.,Ghavimi, Bahman,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Ribadeneira, Maria D.,Vaddi, Krishna,Trzaskos, James,Newton, Robert C.,Duan, James J.-W.,Decicco, Carl P.
, p. 4453 - 4459 (2007/10/03)
Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1- methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl} -5-piperidinecarboxamide) with a sulfonyl group led to a new series of α,β-cyclic and β,β-cyclic γ-sulfonyl hydroxamic acids, which were potent TNF-α converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy-(4S,5S)-1-methyl-5-{[4-(2-methyl-4- quinolinylmethoxy)phenyl]sulfonylmethyl}-4-pyrrolidinecarboxamide) exhibited IC50 values of 1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP-1, -2, -9 and -13 and was orally bioavailable with an F value of 46% in mice.