F-17464

F-17464
Clinical data
Other namesF17464; F-17,464
Routes of
administration		Oral[1]
Drug classDopamine D3 receptor antagonist; Serotonin 5-HT1A receptor agonist
ATC code
  • None
Pharmacokinetic data
Elimination half-life1.32 hours[2][3]
Identifiers
  • N-[3-[4-[4-(8-oxo-[1,3]dioxolo[4,5-g]chromen-7-yl)butyl]piperazin-1-yl]phenyl]methanesulfonamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC25H29N3O6S
Molar mass499.58 g·mol−1
3D model (JSmol)
  • CS(=O)(=O)NC1=CC(=CC=C1)N2CCN(CC2)CCCCC3=COC4=CC5=C(C=C4C3=O)OCO5
  • InChI=1S/C25H29N3O6S/c1-35(30,31)26-19-6-4-7-20(13-19)28-11-9-27(10-12-28)8-3-2-5-18-16-32-22-15-24-23(33-17-34-24)14-21(22)25(18)29/h4,6-7,13-16,26H,2-3,5,8-12,17H2,1H3
  • Key:KLOYLPZTHLSRRB-UHFFFAOYSA-N

F-17464 is a dopamine D3 receptor antagonist and serotonin 5-HT1A receptor partial agonist which was under development for the treatment of schizophrenia but was never marketed.[1][4][2][5][6][3] It is taken orally.[1]

The drug's affinities (Ki) have been found to be 0.17 nM for the dopamine D3 receptor, 0.16 nM for the serotonin 5-HT1A receptor, and 8.9 to 12.1 nM for the dopamine D2 receptor, with more than 50-fold selectivity for the dopamine D3 receptor over the dopamine D2 receptor.[3][2][6] It also shows a much slower dissociation rate from the dopamine D3 receptor than from the dopamine D2 receptor.[6] The drug possesses low affinity for the serotonin 5-HT2A and 5-HT2C receptors (Ki = 437 nM and 1,995 nM, respectively).[2] F-17464 showed more than 80% occupancy of the dopamine D3 receptor and only 20% occupancy of the dopamine D2 receptor with positron emission tomography (PET) imaging in humans.[2][3][5][7] It inhibited amphetamine- and dizocilpine (MK-801)-induced hyperlocomotion in rodents.[5]

F-17464 was first described in the scientific literature by 2015.[8] It was under development by Pierre Fabre.[1][4] The drug reached phase 2 clinical trials for schizophrenia prior to the discontinuation of its development in 2021.[1][4] The findings of a phase 2 trial have been published.[3][2][9]

See also

References

  1. ^ a b c d e "F 17464". AdisInsight. 27 September 2021. Retrieved 9 June 2026.
  2. ^ a b c d e f Lobo MC, Whitehurst TS, Kaar SJ, Howes OD (January 2022). "New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics". Neuroscience and Biobehavioral Reviews. 132: 324–361. doi:10.1016/j.neubiorev.2021.11.032. PMC 7616977. PMID 34838528.
  3. ^ a b c d e Ahmad SR, Zeyaullah M, AlShahrani AM, Khan MS, Dawria A, Mohieldin A, et al. (2025). "Unlocking the potential of lumateperone and novel anti-psychotics for schizophrenia". BioImpacts. 15 30259. doi:10.34172/bi.30259. PMC 11954750. PMID 40161932.
  4. ^ a b c "Delving into the Latest Updates on F-17464 with Synapse". Synapse. 28 March 2026. Retrieved 9 June 2026.
  5. ^ a b c Sokoloff P, Le Foll B (January 2017). "The dopamine D3 receptor, a quarter century later". The European Journal of Neuroscience. 45 (1): 2–19. doi:10.1111/ejn.13390. PMID 27600596.
  6. ^ a b c Cosi C, Martel JC, Auclair AL, Collo G, Cavalleri L, Heusler P, et al. (January 2021). "Pharmacology profile of F17464, a dopamine D3 receptor preferential antagonist". European Journal of Pharmacology. 890 173635. doi:10.1016/j.ejphar.2020.173635. PMID 33065094.
  7. ^ Slifstein M, Abi-Dargham A, Girgis RR, Suckow RF, Cooper TB, Divgi CR, et al. (February 2020). "Binding of the D3-preferring antipsychotic candidate F17464 to dopamine D3 and D2 receptors: a PET study in healthy subjects with [11C]-(+)-PHNO". Psychopharmacology. 237 (2). Berl: 519–527. doi:10.1007/s00213-019-05387-w. PMID 31773210.
  8. ^ Joussot J (24 April 2015). Stratégies de synthèse d'un nouvel antipsychotique potentiel : cascades réactionnelles palladocatalysées : un outil puissant pour la synthèse de structures polycycliques complexes et hautement fonctionnalisées (phdthesis thesis) (in French). Université de Strasbourg. Retrieved 9 June 2026.
  9. ^ Bitter I, Lieberman JA, Gaudoux F, Sokoloff P, Groc M, Chavda R, et al. (October 2019). "Randomized, double-blind, placebo-controlled study of F17464, a preferential D3 antagonist, in the treatment of acute exacerbation of schizophrenia". Neuropsychopharmacology. 44 (11): 1917–1924. doi:10.1038/s41386-019-0355-2. PMC 6785149. PMID 30822774.
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