7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics. 2. Pharmacological profile of 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (Abaperidone, FI-8602)

A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized a nd tested as potential antipsychotics in several in vitro and in vivo assay s. The compounds possessed good affinity for Dp receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high p otency in the climbing mice assay on oral administration, suggesting a pote nt antipsychotic effect as compared to reference standards. Compound 23 was selected for fur ther pharmacological evaluation. induction of catalepsy a nd inhibition of stereotypies weaker than standards, along with a lower inc rease in serum prolactin levels, were indicative of a potential atypical pr ofile for this compound. From these results, 7-[3-[4-(6-fluoro-1,2-benzisox azol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (23, abape ridone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.