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Enantiomeric conformers of the opioid agonist ketobemidone HCl in the crystal state
Author(s) -
Froimowitz Mark,
Cody Vivian
Publication year - 1993
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530050713
Subject(s) - conformational isomerism , chemistry , monoclinic crystal system , enantiomer , stereochemistry , crystal structure , crystallography , agonist , ring (chemistry) , molecule , piperidine , receptor , organic chemistry , biochemistry
Abstract A crystal of the potent opioid agonist ketobemidone [1‐methyl‐4‐(3‐hydroxyphenyl)‐4‐propionylpiperidine] HCl was analyzed by X‐ray crystallography. The crystal was monoclinic, space group P 2 1 /n with four molecules in the unit cell. In agreement with MM2 calculations (J. Med. Chem. 25:1127–1133, 1982), the crystal contains mirror image conformers in which the phenyl ring is equatorial to the piperidine ring. The conformers are enantiomers since they are not superimposable. One conformer is predicted to be responsible for the typical morphine‐like activity of the compound since it closely matches the preferred conformer of the morphine‐like (+)‐phenylmorphan whereas the other conformer resembles the preferred conformers of (+)‐β‐prodine and (−)‐phenylmorphan which have atypical opioid properties and/or structure–activity relationships. The importance of considering the conformational enantiomers of a nonchiral receptor ligand in centrosymmetric crystal structures is emphasized. © 1993 Wiley‐Liss, Inc.