Aminimides as Potential CNS Acting Agents. II Design, Synthesis, and Receptor Binding of 4′-Arylalkyl Aminimide Analogues of Clozapine as Prospective Novel Antipsychotics

We report the synthesis of a series of second generation aminimide-based analogues of clozapine, investigating the length of the linker between the aminimide functional group and the introduced aryl moiety. The chemistry and structural characterization of this series of 4′-arylalkyl aminimide analogues of clozapine are described. Preliminary findings on the biochemical effects of linker length and type of aryl moiety on affinity for dopamine D4 and serotonin 5-HT2A receptors are discussed. All of the compounds showed a marked reduction in binding at the two receptors when compared with clozapine, thus showing a reduced potential for atypical antipsychotic activity.