The stereochemistry and medicinal chemistry of 3-substituted 6,7-benzomorphans.

  • Abiodun O. Ogundaini

Student thesis: Doctoral ThesisPhD


A brief survey of synthetic narcotic analgesics and newer developments in analgesic research is given. In particular, the chemistry and structure-biological-activity relationships in the 6,7-benzomorphan area is reviewed. The higher agonist potency of 4,5-dimethyl-6,7-benzomorphan over the cis-3,5-dimethyl isomer has been attributed tentatively to steric hindrance of the nitrogen lone electron pair in the latter by an equatorial 3-methyl group. A more detailed investigation of this claim is therefore the subject of the present work. A series of 3-monosubstituted and 3,3-disubstituted-6,7-benzomorphans have been synthesized and characterized. The configuration of each is established by 1H and 13C n.m.r. spectroscopy. The differences in analgesic activity is explained by substituent participation in receptor interactions rather than by hindrance of nitrogen non bonding electrons, and this is considered in some detail. 2'-Hydroxyl analogues of 2-alkyl-cis-3,5-dimethyl-6,7-benzomorphan and the corresponding 2,4,5-trimethyl isomer have been prepared and evaluated to complement the data on the 5,9-dimethyl isomers. The inactivity of 2'-hydroxyl-2,4,5-trimethyl-6,7-benzomorphan relative to the non-phenolic analogue has highlighted the need for further investigation in this area since, in general, the observation is that 2'-hydroxyl group leads to enhancement of activity in 6,7-benzomorphans. Some suggestions for additional work are also made. Lastly, some potential analgesics in the 6,7-benzomorphan series having novel 2-amidino substituents have been prepared and at present are being evaluated.
Date of Award1983
Original languageEnglish
Awarding Institution
  • University of Bath

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