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ID: ALA1133791

Journal: Bioorg Med Chem Lett

Title: Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams.

Authors: Macdonald SJ, Dowle MD, Harrison LA, Spooner JE, Shah P, Johnson MR, Inglis GG, Clarke GD, Belton DJ, Smith RA, Molloy CR, Dixon M, Murkitt G, Godward RE, Skarzynski T, Singh OM, Kumar KA, Hodgson ST, McDonald E, Hardy GW, Finch H, Humphreys DC, Fleetwood G.

Abstract: Described are the acylation binding of trans-lactam 1 to porcine pancreatic elastase, the selection of the SO2Me activating group for the lactam N which also confers metabolic stability in hamster liver microsomes, the introduction of aqueous solubility through the piperidine salt 9, the in vivo oral activity of 9 and its bioavailability, and the introduction of 9 as an intracellular neutrophil elastase inhibitor.

CiteXplore: 11206469

DOI: 10.1016/s0960-894x(00)00632-6