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ID: ALA1131344

Journal: Bioorg Med Chem Lett

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

Authors: Pratt LM, Beckett RP, Bellamy CL, Corkill DJ, Cossins J, Courtney PF, Davies SJ, Davidson AH, Drummond AH, Helfrich K, Lewis CN, Mangan M, Martin FM, Miller K, Nayee P, Ricketts ML, Thomas W, Todd RS, Whittaker M.

Abstract: 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 alpha-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 TNF alpha release.

CiteXplore: 9871766

DOI: 10.1016/s0960-894x(98)00218-2