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Discovery of further pyrrolidine trans-lactams as inhibitors of human neutrophil elastase (HNE) with potential as development candidates and the crystal structure of HNE complexed with an inhibitor (GW475151).
Macdonald SJ, Dowle MD, Harrison LA, Clarke GD, Inglis GG, Johnson MR, Shah P, Smith RA, Amour A, Fleetwood G, Humphreys DC, Molloy CR, Dixon M, Godward RE, Wonacott AJ, Singh OM, Hodgson ST, Hardy GW. Macdonald SJ, et al. Among authors: molloy cr. J Med Chem. 2002 Aug 29;45(18):3878-90. doi: 10.1021/jm020881f. J Med Chem. 2002. PMID: 12190311
Syntheses of trans-5-oxo-hexahydro-pyrrolo[3,2-b]pyrroles and trans-5-oxo-hexahydro-furo[3,2-b]pyrroles (pyrrolidine trans-lactams and trans-lactones): new pharmacophores for elastase inhibition.
Macdonald SJ, Belton DJ, Buckley DM, Spooner JE, Anson MS, Harrison LA, Mills K, Upton RJ, Dowle MD, Smith RA, Molloy CR, Risley C. Macdonald SJ, et al. Among authors: molloy cr. J Med Chem. 1998 Oct 8;41(21):3919-22. doi: 10.1021/jm981026s. J Med Chem. 1998. PMID: 9767628 No abstract available.
Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams.
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. Macdonald SJ, et al. Among authors: molloy cr. Bioorg Med Chem Lett. 2001 Jan 22;11(2):243-6. doi: 10.1016/s0960-894x(00)00632-6. Bioorg Med Chem Lett. 2001. PMID: 11206469
The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate.
Macdonald SJ, Dowle MD, Harrison LA, Shah P, Johnson MR, Inglis GG, Clarke GD, Smith RA, Humphreys D, Molloy CR, Amour A, Dixon M, Murkitt G, Godward RE, Padfield T, Skarzynski T, Singh OM, Kumar KA, Fleetwood G, Hodgson ST, Hardy GW, Finch H. Macdonald SJ, et al. Among authors: molloy cr. Bioorg Med Chem Lett. 2001 Apr 9;11(7):895-8. doi: 10.1016/s0960-894x(01)00078-6. Bioorg Med Chem Lett. 2001. PMID: 11294386