B. Gérardy, J. Poupaert, D. Vandervorst
1985
Citations
0
Influential Citations
4
Citations
Journal
Journal of Labelled Compounds and Radiopharmaceuticals
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.