Synthesis and anti-inflammatory activities of N-benzoylamino-1,2,3,6-tetrahydropyridine analogs.

The anti-inflammatory activity of N-benzoylamino-1,2,3,6-tetrahydropyridine (Fig. 1) has been previously described. Further structural modification of 1 indicated that anti-inflammatory activities were greatly influenced by the position and nature of substituents on the tetrahydropyridine ring moiety. Analogs of 1 with benzyl group at position 4 of the tetrahydropyridine ring moiety and substituents on the benzene moiety were synthesized (9a-90). The effect of these substituents on pharmacological activity was screened in vivo using the carrageenan-induced paw edema assay in male Sprague-Dawley rats. Analogs with electron-donating substituents at position 4 and 2 of the benzene moiety 9f, 90 and 9d exhibited significant anti-inflammatory activities, similar to that observed for the reference compound, indomethacin. In summary, at an early stage of efforts to establish structure-activity relationship within this series, we found that 9f is a promising lead compound chosen for further investigation.