6533b825fe1ef96bd12833a2

RESEARCH PRODUCT

Nonsteroidal Antiinflammatory Agents, XVIII: C-5 Functionalized 6,7-Diphenyl-2,3-dihydro-1H-pyrrolizines as Inhibitors of Bovine Cyclooxygenase and 5-Lipoxygenase

subject

description

6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding propionic acid compounds, but they aren't well balanced dual inhibitors as shown for the carboxylic derivatives. A structure activity relationship and the enzyme selectivity are discussed. Nichtsteroidale Antiphlogistika, 18. Mitt.: C-5-funktionalisierte 6,7-Diaryl-2,3-Dihydro-1H-Pyrrolizine als Inhibitoren der Rindercyclooxygenase und 5-Lipoxygenase Die entzundungshemmende Aktivitat von an C-5 funktionalisierten 6-(4-Chlorphenyl)-7-phenyl-dihydro-1H-pyrrolizinen wird beschrieben. Die aus Rinderblut gewonnenen Enzyme Cyclooxygenase und 5-Lipoxygenase werden fur die Testung herangezogen. Das Iminoxyessigsaurederivat sowie das iminotetrazolsubstituierte Dihydropyrrolizin sind equipotent mit der korrespondierenden Propionsaure bezuglich der Inhibierung der 5-Lipoxygenase, sie besitzen jedoch nicht die ausgewogene duale Hemmwirkung der Carbonsaure. Die Hemmung beider Enzyme und die Enzymselektivitat wird in Verbindung mit strukturellen Parametern diskutiert.