Tiflorex: Difference between revisions

Tiflorex
Clinical data
ATC code	none;
Identifiers
	IUPAC name (RS)-N-ethyl-1-{3-[(trifluoromethyl)thio]phenyl}propan-2-amine;
CAS Number	53993-67-2 ;
PubChem CID	173669;
ChemSpider	151574 ;
UNII	EG3B69DFQ5;
CompTox Dashboard (EPA)	DTXSID90866374 ;
Chemical and physical data
Formula	C12H16F3NS
Molar mass	263.32 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES CCNC(C)Cc1cccc(c1)SC(F)(F)F;
	InChI InChI=1S/C12H16F3NS/c1-3-16-9(2)7-10-5-4-6-11(8-10)17-12(13,14)15/h4-6,8-9,16H,3,7H2,1-2H3 ; Key:HNONSDNCRNUTCT-UHFFFAOYSA-N ;
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Revision as of 15:46, 26 July 2023

Tiflorex (TFX), formerly known as flutiorex, is a stimulant^{[citation needed]} amphetamine that was under development as an appetite suppressant in the 1970s^[1]^[2], but appears to have been abandoned.
It is structurally related to fenfluramine and 4-MTA.

Tiflorex went to phase II clinical trials. The extended release formulation "TFX-SR" produced significant suppression of appetite. It also caused slightly more sleep disturbances and headaches than placebo, as well as mydriasis and a self-reported decrease in arousal. It had little effect on heart rate.^[2]

Tifluorex is claimed to be a more potent anorectic than fenfluramine, with twice its potency in humans^[2] and 4 times its potency in rats.^[3]

Pharmacology

Pharmacodynamics

The mechanism of action of tiflorex has apparently never been studied. Similar compounds such as fenfluramine, norfenfluramine and 4-MTA act as selective serotonin releasing agents and 5-HT₂ receptor agonists. Fenfluramine in particular causes very similar side effects and appetite suppression at therapeutically relevant doses.

Pharmacokinetics

In rats, tiflorex is rapidly N-dealkylated to norflutiorex. Both tiflorex and norflutiorex appear to be excreted in urine.^[1]

Synthesis

The Rosenmund reduction of 3-(trifluoromethylthio)benzoyl chloride [51748-28-8] (1) gave 3-((trifluoromethyl)thio)benzaldehyde [51748-27-7] (2). Henry reaction with nitroethane led to 1-(2-nitroprop-1-en-1-yl)-3-[(trifluoromethyl)sulfanyl]benzene [176242-84-5] (3). With the aid of iron catalyst in concentrated HCl acid there occurred FGI into 1-(3'-trifluoromethylthiophenyl)-2-propanone, CID:21325269 (4'). Reductive amination with ethylamine and formic acid as the reductant completed the synthesis of tiflorex (5).

References

^ ^a ^b Giudicelli JF, Richer C, Berdeaux A (February 1976). "Preliminary assessment of flutiorex, a new anorectic drug, in man". British Journal of Clinical Pharmacology. 3 (1): 113–21. doi:10.1111/j.1365-2125.1976.tb00578.x. PMC 1428817. PMID 788737.
^ ^a ^b ^c Silverstone T, Fincham J, Plumley J (April 1979). "An evaluation of the anorectic activity in man of a sustained release formulation of tiflorex". British Journal of Clinical Pharmacology. 7 (4): 353–6. doi:10.1111/j.1365-2125.1979.tb00945.x. PMC 1429648. PMID 444355.
^ Stuart S (2013-09-11). Abstracts: Sixth International Congress of Pharmacology. ISBN 9781483152530.
^ Don P. R. L. Giudicelli & Henry Najer, U.S. patent 4,148,923 (1979 to Synthelabo SA).

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

[br_j_1976-1] Giudicelli JF, Richer C, Berdeaux A (February 1976). "Preliminary assessment of flutiorex, a new anorectic drug, in man". British Journal of Clinical Pharmacology. 3 (1): 113–21. doi:10.1111/j.1365-2125.1976.tb00578.x. PMC 1428817. PMID 788737.

[brjclinpharm-2] Silverstone T, Fincham J, Plumley J (April 1979). "An evaluation of the anorectic activity in man of a sustained release formulation of tiflorex". British Journal of Clinical Pharmacology. 7 (4): 353–6. doi:10.1111/j.1365-2125.1979.tb00945.x. PMC 1429648. PMID 444355.

[3] Stuart S (2013-09-11). Abstracts: Sixth International Congress of Pharmacology. ISBN 9781483152530.

[4] Don P. R. L. Giudicelli & Henry Najer, U.S. patent 4,148,923 (1979 to Synthelabo SA).

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-{{Short description|Stimulant amphetamine}}
+{{Short description|Never marketed appetite suppressant}}
 {{Drugbox
 | Verifiedfields = changed
@@ Line 5: / Line 5: @@
 | verifiedrevid = 449587989
 | IUPAC_name = (''RS'')-''N''-ethyl-1-<nowiki/>{3-[(trifluoromethyl)thio]phenyl}propan-2-amine
-| image = Tiflorex.svg
+| image = Tiflorex standardized.png
 | width = 260px
 | chirality = [[Racemic mixture]]
@@ Line 32: / Line 32: @@
 }}
-'''Tiflorex''', formerly known as '''flutiorex''', is a [[stimulant]] [[amphetamine]]. Its most pronounced effect is in suppression of appetite; it has little effect on pulse rate, sleep, or mood.<ref name="brjclinpharm">{{cite journal | vauthors = Silverstone T, Fincham J, Plumley J | title = An evaluation of the anorectic activity in man of a sustained release formulation of tiflorex | journal = British Journal of Clinical Pharmacology | volume = 7 | issue = 4 | pages = 353–6 | date = April 1979 | pmid = 444355 | pmc = 1429648 | doi = 10.1111/j.1365-2125.1979.tb00945.x }}</ref> It was found to be twice as potent an anorectic as [[fenfluramine]].<ref name="br j 1976">{{cite journal | vauthors = Giudicelli JF, Richer C, Berdeaux A | title = Preliminary assessment of flutiorex, a new anorectic drug, in man | journal = British Journal of Clinical Pharmacology | volume = 3 | issue = 1 | pages = 113–21 | date = February 1976 | pmid = 788737 | pmc = 1428817 | doi = 10.1111/j.1365-2125.1976.tb00578.x }}</ref>
+'''Tiflorex''' (TFX), formerly known as '''flutiorex''', is a [[stimulant]]{{citation needed|date=July 2023}} [[Substituted amphetamine|amphetamine]] that was under development as an [[Anorectic|appetite suppressant]] in the 1970s<ref name="br j 1976">{{cite journal | vauthors = Giudicelli JF, Richer C, Berdeaux A | title = Preliminary assessment of flutiorex, a new anorectic drug, in man | journal = British Journal of Clinical Pharmacology | volume = 3 | issue = 1 | pages = 113–21 | date = February 1976 | pmid = 788737 | pmc = 1428817 | doi = 10.1111/j.1365-2125.1976.tb00578.x }}</ref><ref name="brjclinpharm">{{cite journal | vauthors = Silverstone T, Fincham J, Plumley J | title = An evaluation of the anorectic activity in man of a sustained release formulation of tiflorex | journal = British Journal of Clinical Pharmacology | volume = 7 | issue = 4 | pages = 353–6 | date = April 1979 | pmid = 444355 | pmc = 1429648 | doi = 10.1111/j.1365-2125.1979.tb00945.x }}</ref>, but appears to have been abandoned.<br>
+It is [[Structural analog|structurally related]] to [[Fenfluramine|fenfluramine]] and [[4-Methylthioamphetamine|4-MTA]].
+Tiflorex went to phase II clinical trials. The [[Modified-release dosage|extended release]] formulation "TFX-SR" produced significant suppression of appetite. It also caused slightly more sleep disturbances and [[Headache|headaches]] than placebo, as well as [[Mydriasis|mydriasis]] and a self-reported [[Sedation|decrease in arousal]]. It had little effect on [[Heart rate|heart rate]].<ref name="brjclinpharm"/>
+Tifluorex is claimed to be a more potent anorectic than fenfluramine, with twice its potency in humans<ref name="brjclinpharm"/> and 4 times its potency in rats.<ref>{{Cite book | url=https://books.google.com/books?id=z_8kBQAAQBAJ&pg=PA356 |title = Abstracts: Sixth International Congress of Pharmacology|isbn = 9781483152530|last1 = Stuart|first1 = Sam | name-list-style = vanc |date = 2013-09-11}}</ref>
+== Pharmacology ==
+=== Pharmacodynamics ===
+The mechanism of action of tiflorex has apparently never been studied. Similar compounds such as [[Fenfluramine|fenfluramine]], [[Norfenfluramine|norfenfluramine]] and [[4-Methylthioamphetamine|4-MTA]] act as [[Serotonin releasing agent|selective serotonin releasing agents]] and [[5-HT2 receptor|5-HT<sub>2</sub>]] receptor agonists. Fenfluramine in particular causes very similar side effects and appetite suppression at therapeutically relevant doses.
+=== Pharmacokinetics ===
+In rats, tiflorex is rapidly ''N''-dealkylated to [[Norflutiorex|norflutiorex]]. Both tiflorex and norflutiorex appear to be excreted in urine.<ref name="br j 1976"/>
-SL 72.340-d was cited to be 4x the anorectant potency of fenfluramine (ED50=1.4&nbsp;mg/kg vs 5.6&nbsp;mg/kg).<ref>{{Cite book | url=https://books.google.com/books?id=z_8kBQAAQBAJ&pg=PA356 |title = Abstracts: Sixth International Congress of Pharmacology|isbn = 9781483152530|last1 = Stuart|first1 = Sam | name-list-style = vanc |date = 2013-09-11}}</ref>
 ==Synthesis==
 [[File:Tiflorex synthesis.svg|thumb|500px|center|Patent:<ref>Don P. R. L. Giudicelli & Henry Najer, {{US patent|4148923}} (1979 to Synthelabo SA).</ref>]]
@@ Line 41: / Line 53: @@
 {{reflist}}
-{{Stimulants}}
+{{Anorectics}}
-{{Monoamine releasing agents}}
 {{Phenethylamines}}
 [[Category:Anorectics]]
-[[Category:Trifluoromethyl compounds]]
 [[Category:Substituted amphetamines]]
+[[Category:Abandoned drugs]]
+[[Category:Trifluoromethyl compounds]]
+[[Category:Trifluoromethylthio compounds]]
 [[Category:Thioethers]]

v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine Phenpromethamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-AL 3C-BZ 3C-E 3C-MAL 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA ZDCM-04 Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L-Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D-Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D-DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L-DOPA (Levodopa) L-DOPS (Droxidopa) L-Phenylalanine L-Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101 Venlafaxine