1-Aminoindanes as novel motif with potential atypical antipsychotic properties.

As part of an on-going effort to investigate the chemical space requirements for D(2)/5-HT(2A) receptor antagonists as atypical antipsychotics, new 1-aminoindanes were synthesized. The replacement of the heterocycle (oxindole) in ziprasidone with a carbocycle (indane) was well tolerated and was found to retain binding affinities for dopamine D(2), serotonin 5-HT(2A), and serotonin 5-HT(1A). Such compounds hold promise as a new chemical motif with atypical antipsychotic properties for the treatment of schizophrenia and related disorders.

8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity.

Several new, potent dopamine subtype 2 (DA D(2)) active compounds with serotonin subtype 2A (5-HT(2A)) pharmacology are presented. 8-Substituted 3,4-dihydroquinolinones, tetrahydroquinolines, and N-acyl tetrahydroquinolines were evaluated in primary assays. Subtle changes on this novel scaffold translated to large changes in potency and selectivity in vitro.