Synthesis and pharmacological evaluation of some novel thebaine derivatives: N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine incorporating the 1,3,4-oxadiazole or the 1,3,4-thiadiazole moiety

Abstract

In this study, we synthesized some novel N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine 7α-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as potential analgesic agents. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C NMR, 2D NMR, and high-resolution mass spectral data. The analgesic activity was evaluated by a rat-hot plate test model and a rat tail-flick model. Compound 12 showed analgesic activity higher than that of morphine. In addition to a histopathological and biochemical evaluation, the LD₅₀ dose for the most active compound 12 was determined.