The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis.
A series of potent, competitive and highly selective kynurenine monooxygenase inhibitors have been discovered via a substrate-based approach for the treatment of acute pancreatitis. The lead compound demonstrated good cellular potency and clear pharmacodynamic activity in vivo.
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Electronic address: john.2.liddle@gsk.com.
John
J
Liddle
GlaxoSmithKline, Les Ulis, Paris, France.
Benjamin
B
Beaufils
Centre for Cardiovascular Science, University of Edinburgh, UK.
Margaret
M
Binnie
GlaxoSmithKline, Les Ulis, Paris, France.
Anne
A
Bouillot
GlaxoSmithKline, Les Ulis, Paris, France.
Alexis A
AA
Denis
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Michael M
MM
Hann
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Carl P
CP
Haslam
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Duncan S
DS
Holmes
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Jon P
JP
Hutchinson
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Michael
M
Kranz
Centre for Cardiovascular Science, University of Edinburgh, UK.
Andrew
A
McBride
GlaxoSmithKline, Les Ulis, Paris, France.
Olivier
O
Mirguet
MRC Centre for Inflammation Research, University of Edinburgh, UK.
Damian J
DJ
Mole
EastChem School of Chemistry, University of Edinburgh, UK.
Christopher G
CG
Mowat
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Sandeep
S
Pal
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Paul
P
Rowland
GlaxoSmithKline, Les Ulis, Paris, France.
Lionel
L
Trottet
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Iain J
IJ
Uings
GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Ann L
AL
Walker
Centre for Cardiovascular Science, University of Edinburgh, UK.
Scott P
SP
Webster
D000818:Animals; D001583:Benzoxazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007737:Kynurenine / Q000378:metabolism; D050601:Kynurenine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D014364:Tryptophan / Q000378:metabolism
D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D007191:Indazoles; D007737:Kynurenine; C017057:benzoxazolone; D014364:Tryptophan; D050601:Kynurenine 3-Monooxygenase
Kynurenine; Monooxygenase; Pancreatitis; Substrate; Tryptophan