Benzodiazepine inhibitors of the MMPs and TACE. Part 2.
A series of benzodiazepine MMP/TACE inhibitors bearing polar moieties has been synthesized in an effort to optimize inhibitory activity against LPS-stimulated TNF production in human monocytes and oral activity in a murine LPS model.
Levin
Jeremy I
JI
Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. levinji@wyeth.com
Nelson
Frances C
FC
Delos Santos
Efren
E
Du
Mila T
MT
MacEwan
Gloria
G
Chen
James M
JM
Ayral-Kaloustian
Semiramis
S
Xu
Jun
J
Jin
Guixian
G
Cummons
Terri
T
Barone
Dauphine
D
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009055:Mouth / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001569:Benzodiazepines; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse