223405-99-0Relevant articles and documents
Discovery of γ-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor α converting enzyme: Design, synthesis, and structure-activity relationships
Duan, James J.-W.,Chen, Lihua,Wasserman, Zelda R.,Lu, Zhonghui,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Hardman, Karl D.,Magolda, Ronald L.,Newton, Robert C.,Christ, David D.,Wexler, Ruth R.,Decicco, Carl P.
, p. 4954 - 4957 (2007/10/03)
New γ-lactam TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1′ site as the key area for TACE selectivity over MMPs. Rational exploration of the P1′-S1′ interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1′ group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.
