Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates.
Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates.
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DOI：
10.1016/s0960-894x(03)00514-6
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发表时间：
2003-08
影响因子：
2.7
通讯作者：
J. Levin;J. M. Chen;K. Cheung;D. Cole;C. Crago;E. D. Santos;X. Du;G. Khafizova;G. MacEwan;C. Niu;E. J. Salaski;A. Zask;T. Cummons;A. Sung;J. Xu;Y. Zhang;W. Xu;S. Ayral-Kaloustian;G. Jin;R. Cowling;D. Barone;K. Mohler;R. Black;J. Skotnicki
中科院分区：
文献类型：
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作者：
J. Levin;J. M. Chen;K. Cheung;D. Cole;C. Crago;E. D. Santos;X. Du;G. Khafizova;G. MacEwan;C. Niu;E. J. Salaski;A. Zask;T. Cummons;A. Sung;J. Xu;Y. Zhang;W. Xu;S. Ayral-Kaloustian;G. Jin;R. Cowling;D. Barone;K. Mohler;R. Black;J. Skotnicki
研究了一系列有效的磺酰胺羟酸酯类TACE抑制剂的SAR，它们都含有一个丁酰氧基P1 '基团。特别是，化合物5j对分离的TACE酶和细胞具有优异的体外效力，对MMP-1和MMP-9具有良好的选择性，并且在体内TNF-α生成模型和胶原诱导关节炎模型中具有口服活性。
The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors, all bearing a butynyloxy P1′ group, was explored. In particular, compound 5j has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and MMP-9, and oral activity in an in vivo model of TNF-α production and a collagen-induced arthritis model.