• DOI:10.1021/JM00147A025
• Corpus ID: 1642729

Potential neuroleptic agents. 3. Chemistry and antidopaminergic properties of substituted 6-methoxysalicylamides.

@article{dePaulis1985PotentialNA,
  title={Potential neuroleptic agents. 3. Chemistry and antidopaminergic properties of substituted 6-methoxysalicylamides.},
  author={Tomas de Paulis and Yatendra Kumar and Lars George Johansson and Sten R{\"a}msby and Lennart Florvall and H{\aa}kan Hall and K Angeby-M{\"o}ller and Sven Ove Ogren},
  journal={Journal of medicinal chemistry},
  year={1985},
  volume={28 9},
  pages={
          1263-9
        }
}

• T. de Paulis, Y. Kumar, +5 authors S. Ogren
• Published 1 September 1985
• Chemistry
• Journal of medicinal chemistry

A series of substituted 6-methoxysalicylamides were synthesized from their corresponding 2,6-dimethoxybenzamides by demethylation of one methoxy group with boron tribromide. Substituted 6-methoxysalicylamides having a lipophilic aromatic substituent in the 3-position para with respect to the methoxy group, e.g. a bromo or an iodo atom or an ethyl or a propyl group, and having an (S)-N-(1-alkyl-2-pyrrolidinyl)methyl moiety as the side chain were found to be potent blockers of [3H]spiperone binding in vitro and potent inhibitors of the apomorphine syndrome in the rat. Similar to remoxipride but in contrast to haloperidol, some of the substituted salicylamides show a 10-20-fold separation between the dose that inhibits hyperactivity and that which inhibits stereotypy. It was concluded that, besides the requirement of a lipophilic substituent in the position para to the methoxy group for antidopamine activity in vivo, the formation of a coplanar six-membered pseudoring involving the amide moiety and the methoxy group is a structural requirement for activity in vitro.