Synthesis of monoaryl- and diarylphosphorus analogs of methadone

Article abstract of DOI:10.1021/jm00247a022

Fourteen monoarylphosphorus analogs of methadone belonging to three structural types were synthesized by reacting various chloroalkylamines with the appropriate phosphorus compounds. The phosphorus compounds were selected to vary the steric, electronic, and solubility properties of the final products. Ten diaryl phosphorus analogs of methadone of two structural types were synthesized in a similar manner. The success of the alkylation reaction for both series was markedly affected by the solvent system utilized. Pharmacological screening by the hot plate and acetic writhing methods revealed moderate analgetic activity in some of the compounds apparently related to the lipophilicity of the molecule.