NONSTEROIDAL ANTIINFLAMMATORY AGENTS .28. C-5 FUNCTIONALIZED 6,7-DIPHENYL-2,3-DIHYDRO-1H-PYRROLIZINES AS INHIBITORS OF BOVINE CYCLOOXYGENASE AND 5-LIPOXYGENASE

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.