Tiflorex (TFX), formerly known as flutiorex, is a

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

that was under development as an

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

in the 1970s, but appears to have been abandoned. It is structurally related to

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

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 A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Head ...

than placebo, as well as

mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

and a self-reported decrease in arousal. It had little effect on

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

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

Pharmacology

Pharmacodynamics

The mechanism of action of tiflorex has apparently never been studied. Similar compounds such as

, 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.

Synthesis

The Rosenmund reduction of 3-(trifluoromethylthio)benzoyl chloride 1748-28-8(1) gave 3-((trifluoromethyl)thio)benzaldehyde 1748-27-7(2).

Henry reaction The Henry reaction is a classic carbon–carbon bond formation reaction in organic chemistry. Discovered in 1895 by the Belgian chemist Louis Henry (1834–1913), it is the combination of a nitroalkane and an aldehyde or ketone in the presence ...

with nitroethane led to 1-(2-nitroprop-1-en-1-yl)-3- trifluoromethyl)sulfanylenzene 76242-84-5(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 Ethylamine, also known as ethanamine, is an organic compound with the chemical formula, formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscibility, miscible with virtual ...

and

formic acid Formic acid (), systematically named methanoic acid, is the simplest carboxylic acid. It has the chemical formula HCOOH and structure . This acid is an important intermediate in chemical synthesis and occurs naturally, most notably in some an ...

as the reductant completed the synthesis of tiflorex (5).

References

{{Phenethylamines Anorectics Substituted amphetamines Abandoned drugs Trifluoromethyl compounds Trifluoromethylthio compounds Thioethers