Design and synthesis of an orally active matrix metalloproteinase inhibitor

A series of 4-(4-phenoxy)benzoylamino-4-methoxymethyloxymethyl butyric acid hydroxamates, which were derived from l-glutamic acid, were synthesized and evaluated as matrix metalloproteinase inhibitors. Most of the compounds listed in Table 1, Table 2 and Table 3 exhibited strong inhibitory activity against MMP-2 and MMP-9, as well as even stronger inhibitory activity against MMP-3, but showed relatively weak inhibition of MMP-1. Structure–activity relationships are discussed.

A series of 4-(4-phenoxy)benzoylamino-4-methoxymethyloxymethyl butyric acid hydroxamates were found to exhibit strong inhibitory activity against MMP-2, MMP-9, and MMP-3. Among the compounds tested, 9 showed in vivo activity against MMP-3 after oral administration.Figure optionsDownload as PowerPoint slide