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Modified acidic nonsteroidal anti-inflammatory drugs as dual inhibitors of mPGES-1 and 5-LOX.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2012 Oct 25; Vol. 55 (20), pp. 8958-62. Date of Electronic Publication: 2012 Oct 09. - Publication Year :
- 2012
-
Abstract
- mPGES-1 is a promising target for development of new anti-inflammatory drugs. We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by replacing the carboxylic acid functionality by sulfonamide moieties. Compounds were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC₅₀ = 0.16 μM), while the best 5-LOX inhibition was attained by indomethacin derivative 17 (IC₅₀ = 0.9 μM). Inhibition of COX-1 activity was completely removed.
- Subjects :
- Anti-Inflammatory Agents, Non-Steroidal chemistry
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Cell Line
Humans
Indomethacin analogs & derivatives
Indomethacin chemical synthesis
Indomethacin chemistry
Indomethacin pharmacology
Lipoxygenase Inhibitors chemistry
Lipoxygenase Inhibitors pharmacology
Microsomes drug effects
Microsomes metabolism
Prostaglandin-E Synthases
Pyrazoles chemical synthesis
Pyrazoles chemistry
Pyrazoles pharmacology
Structure-Activity Relationship
Sulfonamides chemistry
Sulfonamides pharmacology
Anti-Inflammatory Agents, Non-Steroidal chemical synthesis
Arachidonate 5-Lipoxygenase metabolism
Intramolecular Oxidoreductases antagonists & inhibitors
Lipoxygenase Inhibitors chemical synthesis
Sulfonamides chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 55
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22992107
- Full Text :
- https://doi.org/10.1021/jm3010543