Trifluperidol: Difference between revisions

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);
Identifiers
	IUPAC name 1-(4-fluorophenyl)-4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]butan-1-one;
CAS Number	749-13-3 ;
PubChem CID	5567;
DrugBank	DB13552 ;
ChemSpider	5366 ;
UNII	R8869Q7R8I;
ChEMBL	ChEMBL15023 ;
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 ; Key:GPMXUUPHFNMNDH-UHFFFAOYSA-N ;

Browse history interactively

← Previous edit

Content deleted Content added

VisualWikitext

Inline

Latest revision as of 21:10, 4 September 2024

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]

Synthesis

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).

References

^ 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.
^ 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.
^ 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.
^ GB895309 idem P. Adriaan J. Janssen, U.S. patent 3,438,991 (1969 to Res Lab Dr C Janssen Nv).
^ 彭响亮, CN 105439811 (2016 to Chengdu Zhongheng Huatie Technology Co Ltd).
^ 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.

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

[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.

[pmid14065098-2] 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.

[pmid14051242-3] 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.

[1]

[2]

[3]

[4]

[5]

[6]

@@ Line 1: / Line 1: @@
+{{short description|Typical antipsychotic}}
 {{Drugbox
+| IUPAC_name = 1-(4-fluorophenyl)-4-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]butan-1-one
-| Verifiedfields = changed
-| verifiedrevid = 470614624
-| IUPAC_name = 1-(4-fluorophenyl)- 4-{4-hydroxy- 4-[3-(trifluoromethyl)phenyl] piperidin-1-yl} butan-1-one
 | image = Trifluperidol.svg
-| width = 200
+| width = 250
 <!--Clinical data-->
-| tradename =
+| tradename =  Triperidol
 | Drugs.com = {{drugs.com|international|trifluperidol}}
 | pregnancy_AU =
 | pregnancy_US =
+| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
+| legal_BR = C1
+| legal_BR_comment = <ref>{{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}}</ref>
+| legal_CA = <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
+| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
+| legal_NZ = <!-- Class A, B, C -->
+| legal_UK = <!-- GSL         / P       / POM / CD / Class A, B, C -->
+| legal_US = <!-- OTC                   / Rx-only  / Schedule I, II, III, IV, V -->
+| legal_EU =
+| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
 | legal_status =
 | routes_of_administration = Oral
@@ Line 21: / Line 30: @@
 <!--Identifiers-->
-| CAS_number_Ref = {{cascite|changed|??}}
+| CAS_number_Ref = {{cascite|correct|CAS}}
 | CAS_number = 749-13-3
 | ATC_prefix = N05
@@ Line 28: / Line 37: @@
 | PubChem = 5567
 | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
-| DrugBank =
+| DrugBank = DB13552
 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
 | ChemSpiderID = 5366
@@ Line 38: / Line 47: @@
 <!--Chemical data-->
 | C=22 | H=23 | F=4 | N=1 | O=2
-| molecular_weight = 409.417 g/mol
 | smiles = FC(F)(F)c1cccc(c1)C3(O)CCN(CCCC(=O)c2ccc(F)cc2)CC3
-| InChI = 1/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
-| InChIKey = GPMXUUPHFNMNDH-UHFFFAOYAW
 | 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
@@ Line 48: / Line 54: @@
 }}
-'''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.
+'''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 symptoms|extrapyramidal]] effects. It is used in the treatment of psychoses including [[mania]] and [[schizophrenia]]. It was discovered at [[Janssen Pharmaceutica]] in 1959.<ref name="pmid14065098">{{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 }}</ref><ref name="pmid14051242">{{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 }}</ref>
-==Chemistry==
+==Synthesis==
+[[File:Trifluperidol synthesis.svg|500px|center|thumb|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0174 Thieme] Patent (claim 9):<ref>GB895309 idem P. Adriaan J. Janssen, {{US Patent|3438991}} (1969 to Res Lab Dr C Janssen Nv).</ref> Precursor:<ref>彭响亮,
-[[File:Trifluperidol Synthesis.png|500px]]
+{{Cite patent|CN|105439811}} (2016 to Chengdu Zhongheng Huatie Technology Co Ltd).</ref> Sila analogue:<ref>{{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}}</ref>]]
-*P. Janssen, J. Adriaan, {{Cite patent|GB|895309}} (1962).
-*P. Janssen, J. Adriaan, {{US Patent|3438991}} (1969).
+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==
+* [[Ocaperidone]]
 == References ==
-{{Reflist|2}}
+{{Reflist}}
-* Gallant DM, Bishop MP, Timmons E, Steele CA, A controlled evaluation of Trifluperidol: a new potent psychopharmacologic agent, Curr Ther Res Clin Exp. 1963 Sep;27:463-71.
-* Gallant DM, Bishop MP, Timmons E, Steele CA, Trifluperidol: a butyrophenone derivative, Am J Psychiatry. 1963 Nov;120:485-7.
 {{Antipsychotics}}
 {{Dopaminergics}}
-[[Category:Piperidines]]
+[[Category:4-Phenylpiperidines]]
-[[Category:Organofluorides]]
+[[Category:Tertiary alcohols]]
 [[Category:Aromatic ketones]]
-[[Category:Alcohols]]
+[[Category:Belgian inventions]]
 [[Category:Butyrophenone antipsychotics]]
 [[Category:Janssen Pharmaceutica]]
-[[Category:Belgian inventions]]
+[[Category:Trifluoromethyl compounds]]
+[[Category:Typical antipsychotics]]
+[[Category:4-Fluorophenyl compounds]]
 {{nervous-system-drug-stub}}
-[[ru:Трифлуперидол]]

v t e Antipsychotics (N05A)
Typical	Butyrophenones: Benperidol Bromperidol Bromperidol decanoate Droperidol Haloperidol^# Haloperidol decanoate Moperone Pipamperone Spiperone Timiperone Trifluperidol Diphenylbutylpiperidines: Fluspirilene Penfluridol Pimozide Phenothiazines: Acepromazine Acetophenazine Butaperazine Carphenazine (carfenazine)^‡ Chlorpromazine Cyamemazine Dixyrazine Fluphenazine Fluphenazine decanoate Fluphenazine enanthate Levomepromazine (methotrimeprazine) Mesoridazine Perazine Periciazine Perphenazine BL-1020 Perphenazine decanoate Perphenazine enanthate Piperacetazine Pipotiazine Pipotiazine palmitate Pipotiazine undecylenate Prochlorperazine Promazine Sulforidazine Thiopropazate Thioproperazine Thioridazine Trifluoperazine Triflupromazine Thioxanthenes: Chlorprothixene Clopenthixol Clopenthixol decanoate Flupentixol Flupentixol decanoate Tiotixene (thiothixene) Zuclopenthixol Zuclopenthixol acetate Zuclopenthixol decanoate
Disputed	Benzamides: Amisulpride Levosulpiride Nemonapride Remoxipride^‡ Sulpiride Sultopride Tiapride Veralipride^‡ Butyrophenones: Melperone Tricyclics: Carpipramine Clocapramine Clorotepine Clotiapine Loxapine Mosapramine Oxyprothepin decanoate Others: Molindone
Atypical	Benzisoxazole/benzisothiazoles: Iloperidone Lurasidone Paliperidone Paliperidone palmitate Perospirone Risperidone^# Ziprasidone Butyrophenones: Lumateperone Phenylpiperazines/quinolinones: Aripiprazole Aripiprazole lauroxil Brilaroxazine^† Brexpiprazole Cariprazine Tricyclics: Asenapine Clozapine^# Olanzapine (+samidorphan) Quetiapine Zotepine Others: Blonanserin Pimavanserin Sertindole
Others	Monoamine-depleting agents: Oxypertine Reserpine Tetrabenazine Muscarinic agonists: Xanomeline/trospium chloride Others/unknown: Azacyclonol
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III