title: The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate.
abstract: The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616A, are described.
authors: Medicinal Chemistry 2, GlaxoWellcome Medicines Research Centre, Stevenage, UK. sjfm5947@glaxowellcome.co.uk
authors: S J
authors: SJ
authors: Macdonald
authors: M D
authors: MD
authors: Dowle
authors: L A
authors: LA
authors: Harrison
authors: P
authors: P
authors: Shah
authors: M R
authors: MR
authors: Johnson
authors: G G
authors: GG
authors: Inglis
authors: G D
authors: GD
authors: Clarke
authors: R A
authors: RA
authors: Smith
authors: D
authors: D
authors: Humphreys
authors: C R
authors: CR
authors: Molloy
authors: A
authors: A
authors: Amour
authors: M
authors: M
authors: Dixon
authors: G
authors: G
authors: Murkitt
authors: R E
authors: RE
authors: Godward
authors: T
authors: T
authors: Padfield
authors: T
authors: T
authors: Skarzynski
authors: O M
authors: OM
authors: Singh
authors: K A
authors: KA
authors: Kumar
authors: G
authors: G
authors: Fleetwood
authors: S T
authors: ST
authors: Hodgson
authors: G W
authors: GW
authors: Hardy
authors: H
authors: H
authors: Finch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001682:Biological Availability; D006224:Cricetinae; D003460:Crystallization; D004285:Dogs; D004355:Drug Stability; D007769:Lactams / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008657:Metabolic Clearance Rate / Q000502:physiology; D010196:Pancreatic Elastase / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism; D015843:Serpins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C119405:GW 311616; D007769:Lactams; D010880:Piperidines; D015843:Serpins; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase