Deoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactions.
Several 3-deoxy opioids and 3,6-dideoxydihydromorphine was 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 antiociceptive 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.
D000700:Analgesics; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D051379:Mice; D009022:Morphine Derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000700:Analgesics; D009022:Morphine Derivatives; D011957:Receptors, Opioid