Synthesis and physico‐chemical properties of (R, S)‐6‐ditrideuteriomethylamino‐4,4‐diphenylheptan‐3‐one hydrochloride (methadone‐d6)

Bruno M. Gérardy, Jacques H. Poupaert, Daniel Vandervorst, Pierre Dumont, Jean‐Pierre ‐P Declerq, Maurice Van Meerssche, Philip S. Portoghese

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A reaction sequence is described to synthesize (R, S)‐6‐ditrideuteriomethylamino‐4,4‐diphenylheptan‐3‐one hydrochloride ( methadone‐d6.HCl ) in 10.5% overall yield starting from dimethylamine‐d6 hydrochloride. While methadone‐d6.HCl had rather similar physicochemical properties compared to methadone.HCl in the solid phase, a divergent behaviour was observed in solution ( pKa, chromatographic and 13C‐NMR data ). A higher basicity along with a more important hydrophilicity were observed for the d6‐derivative. A 13C‐NMR study showed significant differences in the 13C chemical shifts, which were attributed in part to the intrinsic nature of D itself and in part to a conformational perturbation. The longer duration of antinociceptive action, along with higher t1/2 and clearance, and the depression of the metabolic N‐demethylation process were the only biological properties modified by the deuteration.

Original languageEnglish (US)
Pages (from-to)5-22
Number of pages18
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume22
Issue number1
DOIs
StatePublished - Jan 1985

Keywords

  • C‐NMR
  • X‐ray
  • antinociceptive activity
  • deuterium
  • isotopic effects
  • methadone

Fingerprint Dive into the research topics of 'Synthesis and physico‐chemical properties of (R, S)‐6‐ditrideuteriomethylamino‐4,4‐diphenylheptan‐3‐one hydrochloride (methadone‐d<sub>6</sub>)'. Together they form a unique fingerprint.

Cite this