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

Authors
Macdonald, SJF Dowle, MD Harrison, LA Spooner, JE Shah, P Johnson, MR Inglis, GGA Clarke, GDE Belton, DJ Smith, RA Molloy, CR Dixon, M Murkitt, G Godward, RE Skarzynski, T Singh, OMP Kumar, KA Hodgson, ST McDonald, E Hardy, GW Finch, H
Citation
Sjf. Macdonald et al., Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams, BIOORG MED, 11(2), 2001, pp. 243-246
Citations number
9
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
2
Year of publication
2001
Pages
243 - 246
Database
ISI
SICI code
0960-894X(20010122)11:2<243:IIOHNE>2.0.ZU;2-#
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 whi ch also confers metabolic stability in hamster liver microsomes, the introd uction of aqueous solubility through the piperidine salt 9, the in vivo ora l activity of 9 and its bioavailability, and the introduction of 9 as an in tracellular neutrophil elastase inhibitor. (C) 2001 Elsevier Science Ltd. A ll rights reserved.