Trifluperidol

Trifluperidol is a typical antipsychotic of the butyrophenone chemical class. It has general properties similar to those of haloperidol, but is considerably more potent by weight, and causes relatively more severe side effects, especially tardive dyskinesia and other extrapyramidal effects. It is used in the treatment of psychoses including mania and schizophrenia. It was discovered at Janssen Pharmaceutica in 1959.^[2][3]

Trifluperidol

Clinical data
Trade names	Triperidol
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	N05AD02 (WHO)
Legal status
Legal status	BR: Class C1 (Other controlled substances)[1]
Identifiers
IUPAC name 1-(4-fluorophenyl)-4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]butan-1-one
CAS Number	749-13-3 Y
PubChem CID	5567
DrugBank	DB13552 Y
ChemSpider	5366 Y
UNII	R8869Q7R8I
ChEMBL	ChEMBL15023 Y
CompTox Dashboard (EPA)	DTXSID4023703
Chemical and physical data
Formula	C22H23F4NO2
Molar mass	409.425 g·mol−1
3D model (JSmol)	Interactive image
SMILES FC(F)(F)c1cccc(c1)C3(O)CCN(CCCC(=O)c2ccc(F)cc2)CC3
InChI InChI=1S/C22H23F4NO2/c23-19-8-6-16(7-9-19)20(28)5-2-12-27-13-10-21(29,11-14-27)17-3-1-4-18(15-17)22(24,25)26/h1,3-4,6-9,15,29H,2,5,10-14H2 Y Key:GPMXUUPHFNMNDH-UHFFFAOYSA-N Y

Synthesis

Thieme Patent (claim 9):^[4] Precursor:^[5] Sila analogue:^[6]

The Grignard reaction between 1-benzyl-4-piperidone [3612-20-2] (1) and 3-bromobenzotrifluoride [401-78-5] (2) gives 1-benzyl-4-(3-(trifluoromethyl)phenyl)piperidin-4-ol, CID:12718203 (3). Catalytic hydrogenation removes the benzyl protecting group to give 4-[3-(trifluoromethyl)phenyl]-4-piperidinol [2249-28-7] (4). Alkylation with 4-Chloro-4'-fluorobutyrophenone [3874-54-2] (5) introduces the sidechain and hence completed the synthesis of Trifluperidol (6).

See also

• Ocaperidone

References

1. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
2. Gallant DM, Bishop MP, Timmons E, Steele CA (September 1963). "A controlled evaluation of Trifluperidol: a new potent psychopharmacologic agent". Current Therapeutic Research, Clinical and Experimental. 5: 463–71. PMID 14065098.
3. Gallant DM, Bishop MP, Timmons E, Steele CA (November 1963). "Trifluperidol: a butyrophenone derivative". The American Journal of Psychiatry. 120 (5): 485–7. doi:10.1176/ajp.120.5.485. PMID 14051242.
4. GB895309 idem P. Adriaan J. Janssen, U.S. patent 3,438,991 (1969 to Res Lab Dr C Janssen Nv).
5. 彭响亮, CN 105439811 (2016 to Chengdu Zhongheng Huatie Technology Co Ltd).
6. Tacke, R., Nguyen, B., Burschka, C., Lippert, W. P., Hamacher, A., Urban, C., Kassack, M. U. (12 April 2010). "Sila-Trifluperidol, a Silicon Analogue of the Dopamine (D 2 ) Receptor Antagonist Trifluperidol: Synthesis and Pharmacological Characterization". Organometallics. 29 (7): 1652–1660. doi:10.1021/om901011t.