DEOXYMORPHINES - ROLE OF THE PHENOLIC HYDROXYL IN ANTINOCICEPTION AND OPIATE RECEPTOR INTERACTIONS

Several 3-deoxy opioids and 3, 6-dideoxydihydromorphine were synthesized to ascertain the effect of the phenolic hydroxyl group on antinociceptive potency and receptor binding affinity. Catalytic reduction of the 3-tetrazolyl ether derivatives of dihydromorphine provided the entry into the 3-deoxydihydro series. The prototype, 3-deoxymorphine, was prepared by lithium aluminum hydride reduction of 3-deoxy-N-carbethoxymorphinone, obtained via its 7-(phenylseleno) derivative. 3-Deoxydihydromorphinone and 3, 6-dideoxydihydromorphine were found to be about as potent as, or more potent than, morphine in standard antinociceptive assays. Each of them, however, was less potent than the comparable 3-hydroxy analogue, and their binding affinity to the opiate receptor was substantially decreased. The epoxy ring in 3, 6-dideoxydihydromorphine was found to increase the antinociceptive potency of the compound. © 1979, American Chemical Society. All rights reserved.