6533b870fe1ef96bd12cfdf7
RESEARCH PRODUCT
Cyclooxygenase-1/2 (COX-1/COX-2) and 5-lipoxygenase (5-LOX) inhibitors of the 6,7-diaryl-2,3-1H-dihydropyrrolizine type
Holger UlbrichGerd DannhardtBernd L. Fiebichsubject
Blood PlateletsRadioimmunoassayHigh-performance liquid chromatographyIsozymeMonocytesDrug DiscoverymedicineCox 1 cox 2AnimalsHumansMoietyStructure–activity relationshipPyrrolesPlateletLipoxygenase InhibitorsEnzyme InhibitorsChromatography High Pressure LiquidPharmacologychemistry.chemical_classificationbiologyChemistryOrganic ChemistryMembrane ProteinsGeneral MedicineIn vitroIsoenzymesmedicine.anatomical_structureEnzymeBiochemistryCyclooxygenase 2Prostaglandin-Endoperoxide SynthasesEnzyme inhibitorDrug DesignArachidonate 5-lipoxygenaseCyclooxygenase 1biology.proteinCattleCyclooxygenaseNucleusdescription
A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and RIA for COX-2. The balance between COX-1/COX-2 and 5-LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6- and 7-position of the pyrrolizine nucleus. Structure-activity relationships are discussed.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-05-20 | European Journal of Medicinal Chemistry |