1.
Bioorg Med Chem Lett
; 11(22): 2907-10, 2001 Nov 19.
Article
in English
| MEDLINE
| ID: mdl-11677124
ABSTRACT
Modification of the P(1)' substituent of macrocyclic matrix metalloproteinase (MMP) inhibitors provided compounds that are selective for inhibition of tumor necrosis factor-alpha converting enzyme (TACE) over MMP-1 and MMP-2. Several analogues potently inhibited the release of TNF-alpha in a THP-1 cellular assay. Compounds containing a trimethoxyphenyl group in the P(1)' substituent demonstrated TACE selectivity across several series of hydroxamate-based inhibitors.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Hydroxamic Acids/chemical synthesis , Metalloendopeptidases/antagonists & inhibitors , ADAM Proteins , ADAM17 Protein , Enzyme Inhibitors/pharmacology , Hydroxamic Acids/pharmacology , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/metabolism
2.
