Thioketene S-methylide was found to be generated by release of disiloxane from α-(trimethylsilyl)vinyl (trimethylsilyl)methyl sulfoxide and its 1,3-cycloaddition provided a novel method for synthesis of 2-alkylidenetetrahydrothiophenes.
Conversion of potent MMP inhibitors into selective TACE inhibitors
作者:Robert J. Cherney、Bryan W. King、John L. Gilmore、Rui-Qin Liu、Maryanne B. Covington、James J.-W. Duan、Carl P. Decicco
DOI:10.1016/j.bmcl.2005.10.078
日期:2006.2
Novel sultam hydroxamates with potent MMP activity were transformed into potent TACE inhibitors, lacking MMP activity. To accomplish this we relied on structural differences between the MMP and TACE Sl' pockets and the known advantageous tit of a 2-methyl-4-quinolinylmethoxyphenyl group into this region. From this approach, compound 7d was identified as a potent TACE inhibitor (IC50 = 3.7 nM) that lacked MMP-1, -2, -9, and -13 activity. (c) 2005 Elsevier Ltd. All rights reserved.