Trifluperidol
{{short description|Typical antipsychotic}}
{{Drugbox
| IUPAC_name = 1-(4-fluorophenyl)-4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]butan-1-one
| image = Trifluperidol.svg
| image_class = skin-invert-image
| width = 250
| tradename = Triperidol
| Drugs.com = {{drugs.com|international|trifluperidol}}
| pregnancy_AU =
| pregnancy_US =
| legal_AU =
| legal_BR = C1
| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}
| legal_CA =
| legal_DE =
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| legal_US =
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| legal_status =
| routes_of_administration = Oral
| bioavailability =
| metabolism =
| elimination_half-life =
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 749-13-3
| ATC_prefix = N05
| ATC_suffix = AD02
| ATC_supplemental =
| PubChem = 5567
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB13552
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5366
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = R8869Q7R8I
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 15023
| C=22 | H=23 | F=4 | N=1 | O=2
| smiles = FC(F)(F)c1cccc(c1)C3(O)CCN(CCCC(=O)c2ccc(F)cc2)CC3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GPMXUUPHFNMNDH-UHFFFAOYSA-N
}}
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.{{cite journal | vauthors = Gallant DM, Bishop MP, Timmons E, Steele CA | title = A controlled evaluation of Trifluperidol: a new potent psychopharmacologic agent | journal = Current Therapeutic Research, Clinical and Experimental | volume = 5 | pages = 463–71 | date = September 1963 | pmid = 14065098 }}{{cite journal | vauthors = Gallant DM, Bishop MP, Timmons E, Steele CA | title = Trifluperidol: a butyrophenone derivative | journal = The American Journal of Psychiatry | volume = 120 | issue = 5| pages = 485–7 | date = November 1963 | pmid = 14051242 | doi = 10.1176/ajp.120.5.485 }}
Synthesis
[[File:Trifluperidol synthesis.svg|class=skin-invert-image|500px|center|thumb|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0174 Thieme] Patent (claim 9):GB895309 idem P. Adriaan J. Janssen, {{US Patent|3438991}} (1969 to Res Lab Dr C Janssen Nv). Precursor:彭响亮,
{{Cite patent|CN|105439811}} (2016 to Chengdu Zhongheng Huatie Technology Co Ltd). Sila analogue:{{cite journal | vauthors=((Tacke, R.)), ((Nguyen, B.)), ((Burschka, C.)), ((Lippert, W. P.)), ((Hamacher, A.)), ((Urban, C.)), ((Kassack, M. U.)) | journal=Organometallics | title=Sila-Trifluperidol, a Silicon Analogue of the Dopamine (D 2 ) Receptor Antagonist Trifluperidol: Synthesis and Pharmacological Characterization | volume=29 | issue=7 | pages=1652–1660 | date=12 April 2010 | doi=10.1021/om901011t}}]]
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, [https://pubchem.ncbi.nlm.nih.gov/compound/12718203 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
References
{{Reflist}}
{{Antipsychotics}}
{{Dopaminergics}}
Category:Butyrophenone antipsychotics
Category:Janssen Pharmaceutica
Category:Trifluoromethyl compounds