409107-68-2Relevant articles and documents
Conversion of potent MMP inhibitors into selective TACE inhibitors
Cherney, Robert J.,King, Bryan W.,Gilmore, John L.,Liu, Rui-Qin,Covington, Maryanne B.,Duan, James J.-W.,Decicco, Carl P.
, p. 1028 - 1031 (2007/10/03)
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 S1′ pockets and the known advantageous fit of a 2-methyl
Sultam hydroxamates as novel matrix metalloproteinase inhibitors
Cherney, Robert J.,Mo, Ruowei,Meyer, Dayton T.,Hardman, Karl D.,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Wasserman, Zelda R.,Christ, David D.,Trzaskos, James M.,Newton, Robert C.,Decicco, Carl P.
, p. 2981 - 2983 (2007/10/03)
In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (MMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.
