Nitrogen-bridged conformationally constrained etorphine analogs. Synthesis and biological evaluation

Publisher Website
Google Scholar
Abstract
Three N-C8-bridged analogues 4-6 of the opiate etorphine (3) were synthesized and evaluated for opiate agonism and antagonism in rats. In each case ring closure was effected by intramolecular N-alkylation with a suitably developed C8 side chain. Another key synthetic step was the selective monoprotection of diol 11, which allowed independent elaborations of the C7 and C8 side chains. All three analogues showed distinctly diminished agonist activities when compared to the corresponding N-methyl compound, 19(R)-n-butylorvinol (3). Furthermore, no antagonist activity was detectable. The results demonstrate that the conformation at the amino nitrogen in rigid morphinans is critical for potent opiate activity.

This publication has 4 references indexed in Scilit: