The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate.
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.
Macdonald
S J
SJ
Medicinal Chemistry 2, GlaxoWellcome Medicines Research Centre, Stevenage, UK. sjfm5947@glaxowellcome.co.uk
Dowle
M D
MD
Harrison
L A
LA
Shah
P
P
Johnson
M R
MR
Inglis
G G
GG
Clarke
G D
GD
Smith
R A
RA
Humphreys
D
D
Molloy
C R
CR
Amour
A
A
Dixon
M
M
Murkitt
G
G
Godward
R E
RE
Padfield
T
T
Skarzynski
T
T
Singh
O M
OM
Kumar
K A
KA
Fleetwood
G
G
Hodgson
S T
ST
Hardy
G W
GW
Finch
H
H
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*
C119405:GW 311616; D007769:Lactams; D010880:Piperidines; D015843:Serpins; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase