Nonsteroidal anti-inflammatory drugs as scaffolds for the design of 5-lipoxygenase inhibitors.
Representative nonsteroidal anti-inflammatory drug (NSAID) cyclooxygenase inhibitors such as ibuprofen, naproxen, and indomethacin were used as orally bioavailable scaffolds to design selective 5-lipoxygenase (5-LO) inhibitors. Replacement of the NSAID carboxylic acid group with a N-hydroxyurea group provided congeners with selective 5-LO inhibitory activity.
Kolasa
T
T
Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Brooks
C D
CD
Rodriques
K E
KE
Summers
J B
JB
Dellaria
J F
JF
Hulkower
K I
KI
Bouska
J
J
Bell
R L
RL
Carter
G W
GW
D000707:Anaphylaxis / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives; D007052:Ibuprofen / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D017999:Leukotriene E4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009288:Naproxen / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011994:Recombinant Proteins; D009288:Naproxen; D017999:Leukotriene E4; D007052:Ibuprofen; D006918:Hydroxyurea; D007213:Indomethacin