Author/Authors :
James Holms، نويسنده , , Katherine Mast، نويسنده , , Patrick Marcotte، نويسنده , , Ildiko Elmore، نويسنده , , Junling Li، نويسنده , , Lori Pease، نويسنده , , Keith Glaser، نويسنده , , Douglas Morgan، نويسنده , , Michael Michaelides، نويسنده , , Steven Davidsen، نويسنده ,
Abstract :
Modification of the P1′ substituent of macrocyclic matrix metalloproteinase (MMP) inhibitors provided compounds that are selective for inhibition of tumor necrosis factor-α converting enzyme (TACE) over MMP-1 and MMP-2. Several analogues potently inhibited the release of TNF-α in a THP-1 cellular assay. Compounds containing a trimethoxyphenyl group in the P1′ substituent demonstrated TACE selectivity across several series of hydroxamate-based inhibitors.
