Abstract：
:A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for D2 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 potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for further pharmacological evaluation. Induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl )chromen- 4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Bolós J,Anglada L,Gubert S,Planas JM,Agut J,Príncep M,De la Fuente N,Sacristán A,Ortiz JAdoi
10.1021/jm9810396subject
Has Abstractpub_date
1998-12-31 00:00:00pages
5402-9issue
27eissn
0022-2623issn
1520-4804pii
jm9810396journal_volume
41pub_type
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