Design and synthesis of an orally active matrix metalloproteinase inhibitor

Abstract 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 Tables 1–3 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.