Benzomorphans structure-activity-relationships

Grauert, M., Bechtel, W. D., Ensinger, H. A., Merz, H., Carter, A. J. Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as antagonists of the NMDA receptor-channel complex, J. Med. Chem. 1997, 40, 2922-2930... 

Apart from a few notable exceptions (see later), all known narcotic antagonists are based on the morphine, morphinan, or benzomorphan polycyclic systems, that is, on three closely related groups of opioid ligands that share many structure-activity relationships (see Chapters 2, 3, and 4). Details of antagonist representatives of each group will now be given, chiefly confined to N- allyl and N-cyclopropylmethy 1 (CPM) derivatives, with minimal chemical details. 

Work on the relationship between chemical structure and pharmacological activity of morphinans to 1966 has been reviewed by Hellerbach et al. s) and morphinans with antagonist properties were reviewed in 1973.(158) As is the case for 4,5-epoxymorphinans (Chapter 2) and benzomorphans (Chapter 4), molecular geometry is the major structure-biological activity influence, although the nature of the N-substituent imparts significant qualitative and quantitative variations in morphinan pharmacology. 

The model adequately accommodates most structural variants of morphine and the morphinan and benzomorphan groups of analgesic. All such ligands are closely related in the molecular shape and absolute configurational relationships of the more active antipodal forms. Additional receptor sites are required to interact with ... 

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