Chemistry:F-15063

F-15063

Names
Preferred IUPAC name N-{[3-(Cyclopent-1-en-1-yl)phenyl]methyl}-2-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]ethan-1-amine
Other names F-15,063
Identifiers
CAS Number	680203-70-7
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL218261
ChemSpider	8423646
PubChem CID	10248159
UNII	115OSL8W3F
InChI InChI=1S/C24H29NO2/c1-24(2)16-21-11-6-12-22(23(21)27-24)26-14-13-25-17-18-7-5-10-20(15-18)19-8-3-4-9-19/h5-8,10-12,15,25H,3-4,9,13-14,16-17H2,1-2H3 Key: RAIDOKRWKAIHOH-UHFFFAOYSA-N
SMILES CC1(CC2=C(O1)C(=CC=C2)OCCNCC3=CC=CC(=C3)C4=CCCC4)C
Properties
Chemical formula	C24H29NO2
Molar mass	363.49 g mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

F-15,063 is an orally active potential antipsychotic, and an antagonist at the D₂/D₃ receptors, partial agonist at the D₄ receptor, and agonist at the 5-HT_1A receptors. It has greater efficacy at the 5-HT_1A receptors than other antipsychotics, such as clozapine, aripiprazole, and ziprasidone. This greater efficacy may lead to enhanced antipsychotic properties, as antipsychotics that lack 5-HT_1A affinity are associated with increased risk of extrapyramidal symptoms, and lack of activity against the negative symptoms of schizophrenia.

As expression of immediate-early gene (IEG) in certain brain regions may represent markers of anti-psychotic activity, expression of immediate-early gene mRNA in the prefrontal cortex and striatum was measured. Treatment with F-15,063 resulted in induction of c-fos and fosB mRNA expression in the prefrontal cortex. In the striatum, F-15,063 treatment resulted in induction of all IEGs studied (c-fos, fosB, zif268, c-jun, junB, nor1, nur77, arc).

F-15,063 was tested in several animal models that predict antipsychotic activity to help determine the behavioral profile. Administration of F-15,063 blocked amphetamine and ketamine induced hyperlocomotion, but did not affect baseline, spontaneous locomotor activity. In addition, F-15,063 did not produce catalepsy, a side effect of other antipsychotics, such as haloperidol. This inhibition of catalepsy is 5-HT_1A receptor mediated, as pretreatment with the 5-HT_1A antagonist WAY-100635 reinstated catalepsy. The level of catalepsy did not increase with chronic dosing, and there was no evidence for serotonin syndrome at clinically relevant doses.

Plasma levels of F-15,063 decreased seven-fold 4 hours after oral administration, and 25-fold after 8 hours. Despite this, there was still a high (65%) level of central D2 occupancy at 4 hours, and it retained its full antipsychotic potential at this time point. Even after 8 hours, F-15,063 still demonstrated some central D2 occupancy, and retained some antipsychotic activity.