Huang Adrian, Joseph-McCarthy Diane, Lovering Frank, Sun Linhong, Wang Weiheng, Xu Weixin, Zhu Yi, Cui Junqing, Zhang Yuhua, Levin Jeremy I
Chemical and Screening Sciences, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA.
Bioorg Med Chem. 2007 Sep 15;15(18):6170-81. doi: 10.1016/j.bmc.2007.06.031. Epub 2007 Jun 20.
A series of beta-sulfonyl hydroxamate TACE inhibitors, bearing a butynylamino or a butynyloxy P1' group, was designed and synthesized. Of the compounds investigated, 22 has excellent potency against isolated TACE enzyme, shows good selectivity over MMP-2 and MMP-13, and oral activity in an in vivo mouse model of TNF-alpha production.
设计并合成了一系列带有丁炔基氨基或丁炔氧基P1'基团的β-磺酰基异羟肟酸TACE抑制剂。在所研究的化合物中，22对分离的TACE酶具有优异的活性，对MMP-2和MMP-13表现出良好的选择性，并且在TNF-α产生的体内小鼠模型中具有口服活性。
