ABSTRACT
Analogs of the prodine analgesics were prepared and tested for analgesic activity. A good correlation seems to exist between the energy level of the highest occupied molecular orbital and biological activity. The energy level of the highest occupied molecular orbital of the aryl moiety of these analogs may permit a charge transfer interaction between the aryl groups of the analgesic molecules and their receptors with the aryl groups acting as charge donors.
Subject(s)
Alphaprodine/analogs & derivatives , Receptors, Drug/metabolism , Alphaprodine/metabolism , Alphaprodine/pharmacology , Analgesics , Animals , Chemical Phenomena , Chemistry, Physical , Electrochemistry , Mice , Reaction Time/drug effectsABSTRACT
Phenylsalicylate was nitrated to obtain two nitro isomers, which were separated and reduced to the corresponding amines followed by acetylation to give phenyl-5- or phenyl-3-acetamidosalicylate. Phenyl-5-acetamidosalicylate displayed analgesic activity comparable to that of aspirin and phenacetin at doses of 25-50 mg/kg sc and was much less toxic than the latter compounds. Phenyl-3-acetamidosalicylate, however, was ineffective at a similar dose range and caused restlessness at larger doses.
