Abstract
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.
MeSH terms
-
Anaphylaxis / drug therapy
-
Anaphylaxis / metabolism
-
Animals
-
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
-
Anti-Inflammatory Agents, Non-Steroidal / chemistry*
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
-
Cyclooxygenase Inhibitors / chemical synthesis
-
Cyclooxygenase Inhibitors / pharmacology
-
Drug Design
-
Humans
-
Hydroxyurea / analogs & derivatives
-
Ibuprofen / chemistry
-
Indomethacin / chemistry
-
Leukocytes / drug effects
-
Leukocytes / metabolism
-
Leukotriene E4 / metabolism
-
Lipoxygenase Inhibitors* / chemical synthesis*
-
Lipoxygenase Inhibitors* / chemistry
-
Lipoxygenase Inhibitors* / pharmacokinetics
-
Lipoxygenase Inhibitors* / pharmacology
-
Magnetic Resonance Spectroscopy
-
Male
-
Naproxen / chemistry
-
Rats
-
Rats, Sprague-Dawley
-
Recombinant Proteins / metabolism
-
Tumor Cells, Cultured
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Cyclooxygenase Inhibitors
-
Lipoxygenase Inhibitors
-
Recombinant Proteins
-
Naproxen
-
Leukotriene E4
-
Ibuprofen
-
Hydroxyurea
-
Indomethacin