Conformational Properties of 3-Phenylpiperidine and 3-Phenylpyrrolidine Opioid Analgesics

✍ Scribed by Mark Froimowitz

• Book ID: 102880683
• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 874 KB
• Volume: 7
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/jcc.540070414

✦ Synopsis

Conformational energy calculations have been performed on 3-phenylpiperidine and 3-phenylpyrrolidine opioids using the MM2 method. Phenyl equatorial conformers were found to be preferred for 1,2,3-trimethyl-3-phenylpiperidines while phenyl axial conformers were preferred for the 2-demethyl derivative and 1-methyl-3-isobutyl-3-phenylpyrrolidine. These conformational differences may account for differences in their structure-activity relationships. The geometries of these compounds were superimposed onto a rigid phenyl-axial opioid with the result that the more active antipodes of alpha-2,3dimethyl-3-phenylpiperidine and 3-isobutyl-3-phenylpyrrolidine antagonists were found to be a better fit. However, for the beta derivative, which has not yet been resolved, the opposite antipode was found to be a better fit though the orientation of NH bond was quite different. There is a good agreement between the computed molecular geometries and those observed by x-ray crystallography.