The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement

Article abstract of DOI:10.1016/S0960-894X(98)00218-2

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an α-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNFα release.