Abstract
Compound 2, which represents a structurally simplified congener of norbinaltorphimine 1a, was synthesized in order to evaluate the role of its second basic nitrogen in conferring κ-opioid receptor antagonist selectivity. Congener 2 was found to be at least twice as selective as la as a κ antagonist, while its N-carbobenzoxy derivative (3) was inactive at κ-receptors. This study establishes the importance of the second basic nitrogen of la for κ-receptor recognition. It is proposed that this basic group mimics the guanidinium moiety of Arg7, which may be the key κ-address component of dynorphin.
Original language | English (US) |
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Pages (from-to) | 2412-2415 |
Number of pages | 4 |
Journal | Journal of medicinal chemistry |
Volume | 36 |
Issue number | 16 |
DOIs | |
State | Published - Jan 1 1993 |