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

6‐(4‐Chlorophenyl)‐7‐phenyl‐2,3‐dihydro‐1 H ‐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.