Synthesis, Opioid Receptor Binding Profile, and Antinociceptive Activity of 1-Azaspirodecan-10-yl Amides

Article abstract of DOI:10.1021/jm00126a019

A series of azaspiro<4.5>decanyl amides were prepared by a novel cyclization route and examined for opiate receptor binding and antinociceptive activity.Selected tertiary amides in this series showed potent selective μ-receptor binding and antinociceptive activity, in contrast to the less conformationally restricted secondary amides, which showed relatively weak activity.Although structurally similar to the κ-agonist U-50488H (1), these compounds showed virtually no tendency to bind to the κ-receptor.An X-ray crystal structure of compound (21) confirms that the spirocyclic amine does not cause distortion away from the chair conformation of the cyclohexane ring.Either this receptor has very specific requirements for the orientation of the two nitrogens of these compounds or this ring system fills a portion of space more readily tolerated by the μ- and ?-receptors.