458-24-2

Usage

Uses

Used in Pharmaceutical Industry:
Fenfluramine is used as an anorexic agent for suppressing appetite, particularly for carbohydrates. It was previously utilized in the treatment of diabetes and obesity. However, it was withdrawn worldwide due to reports of heart valve disease and pulmonary hypertension associated with its use.
Please note that Fenfluramine has been withdrawn from the market due to its severe side effects, and its use is no longer recommended.

Originator

Obenon,Neofarma

Manufacturing Process

38.5 parts of (trifluoromethyl-3'-phenyl)-1-oximino-2-propane in 550 parts of ethanol (with ammonia) was hydrogenated under pressure of hydrogen 90 kg with a catalyst nickel Reney (20 parts). After a completion of reaction to the reaction mixture was added 1000 parts of water and 300 parts of hydrochloric acid. The mixture was concentrated in vacuo and extracted with 450 parts of ether. To an aqueous phase was added the sodium carbonate and the mixture was extracted with 500 parts of ether. Organic phase was concentrated in vacuo to obtain 29 g of 1-(meta-trifluoromethyl-phenyl)-2-ethylaminopropane. B.P. 96°C at 17 mm.

Therapeutic Function

Anorexic

World Health Organization (WHO)

Fenfluramine, dexfenfluramine and phentermine were approved individually more than 20 years ago in the USA for single-drug, short-term treatment of obesity. The manufacturers of fenfluramine and dexfenfluramine have since voluntarily withdrawn both products from the market worldwide. Phentermine remains available.

InChI:InChI=1/C12H16F3N/c1-3-16-9(2)7-10-5-4-6-11(8-10)12(13,14)15/h4-6,8-9,16H,3,7H2,1-2H3

Upstream product

• 21906-39-8 3-(trifluoromethyl)phenylacetone 
• 75-04-7 ethylamine 
• 1813-96-3 3-<3-(trifluoromethyl)phenyl>propene 
• 351-35-9 3-(trifluoromethyl)phenylacetic acid 
• 2338-76-3 3-trifluoromethylphenylacetonitrile 
• 98-16-8 3-trifluoromethylaniline 
• 557-66-4 ethanamine hydrochloride 
• 154309-36-1 cis-1-<3-(trifluoromethyl)phenyl>propene 
• 154309-40-7 3-ethylamino-1-<3-(trifluoromethyl)phenyl>propan-2-ol 
• 713-71-3 2-<3-(trifluoromethyl)benzyl>oxirane 
• 1886-26-6 norfenfluramine 
• 58879-30-4 trans-1-<3-(trifluoromethyl)phenyl>propene 
• 401-78-5 3-bromo-1-trifluoromethylbenzene 
• 59287-43-3 1-ethyl-2-<3-(trifluoromethyl)benzyl>aziridine 

Downstream Products

• 94593-26-7 C₁₉H₂₀F₃NO₂ 
• 404-82-0 dl-fenfluramine hydrochloride 
• 94593-25-6 C₂₁H₂₄F₃NO₄ 
• 94593-30-3 C₁₄H₁₈F₃NO₂ 

Relevant academic research and scientific papers

NEW METHOD FOR SYNTHESIS OF FENFLURAMINE, AND NEW COMPOSITIONS COMPRISING IT

A new process for preparing the fenfluramine molecule and new compositions containing fenfluramine obtainable with the claimed process.

FENFLURAMINE COMPOSITIONS AND METHODS OF PREPARING THE SAME

Methods of preparing a fenfluramine active pharmaceutical ingredient are provided. Aspects of the method include (a) hydrolyzing a 2-(3-(trifluoromethyl)phenyl)acetonitrile composition to produce a 2-(3-(trifluoromethyl)phenyl)acetic acid composition; (b) reacting the 2-(3-(trifluoromethyl)phenyl)acetic acid composition with acetic anhydride and a catalyst to produce a 1-(3-(trifluoromethyl)phenyl)propan-2-one composition; and (c) reductively aminating the 1-(3-(trifluoromethyl)phenyl)propan-2-one composition with ethylamine using a borohydride reducing agent to produce a fenfluramine composition. Also provided are compositions and pharmaceutical ingredients prepared according to the subject methods including a pharmaceutically acceptable salt of fenfluramine and having less than 0.2% by weight in total of trifluoromethyl regioisomers.

Epoxides, amino alcohols, and aziridines as key intermediates in the asymmetric synthesis of (S)-fenfluramine

The epoxides 3E, 3Z and 8 were obtained from the isomeric alkenes 2E, 2Z and 7.The epoxides were ring-opened by ethylamine in ethanol yielding mixtures of the amino alcohols 4E and 11E, 4T and 11T, and 9, respectively, which were transformed into the aziridines 5trans, 5cis and 12.The regiospecific Pd/C-catalyzed reduction of these aziridines gave fenfluramine 1.The three epoxides 3trans, 3cis and 8 were reduced regiospecifically into 1-propan-2-ol 6, a potent precursor to fenfluramine 1.The validity of our method for asymmettric synthesis has been demonstrated by a synthesis of (S)-fenfluramine 1 starting from the amino alcohol (S)-9.Keyword - fenfluramine / asymmetric synthesis / epoxide / amino alcohol / aziridine / regiospecific catalytic hydrogenation / 1-propan-2-ols

Syntheses of (S)-fenfluramine from (R) or (S)-1-propan-2-ol

(R) and (S)-1-propan-2-ol 3 are useful intermediates in the synthesis of fenfluramine (S)-1.They can be obtained from optically active propylene oxide (R) or (S)-7.The alcohol (R)-3 was transformed in two steps into (S)-fenfluramine using the action of ethylamine on a sulfonate (R)-4.We describe a new one-pot synthesis for (S)-fenfluramine from the azide (S)-5, which was obtained from the alcohol (R)-3 in two steps.We also propose an original and rapid procedure to transform the alcohol (S)-3 into (S)-fenfluramine via the chloride (R)-14 and the azide (S)-5, without preliminary inversion of the alcohol.All of these reactions have been achieved without any loss of chirality.Keywords - 1-propan-2-ol / fenfluramine / asymmetric synthesis / chiral methyloxirane / nucleophilic substitution

Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents

A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.

Reductive Amination of Ketones and Aldehydes at the Mercury-Cathode

Secondary amines are prepared in good yields by potential-controlled reduction of aldehydes or ketones at a mercury cathode in an aqueous solution containing a primary amine.For cyclic ketones, high diastereoselectivities are obtained in some cases.

Means and method for aiding individuals to stop smoking

Individuals are aided in their desire to stop tobacco smoking and lose overweight by administering internally a combination of pharmaceuticals comprising an imidazoline derivative, such as clonidine hydrochloride, with an anorectic, such as phentermine resin.

Phenylalkylamines and phenylalkylureas in combinations to suppress gastric bleeding in aspirin therapy

Novel pharmaceutical methods, combinations and compositions for reducing gastric bleeding during aspirin therapy for inflammation are disclosed. Compounds used in combination with aspirin are phenylalkylamines and phenylalkylureas having the formula: STR1 wherein Z is selected from the group consisting of --NHR2 or STR2 and R is selected from the group consisting of hydrogen, halogen, lower-alkoxy and trifluoromethyl and R1, R2, R3 and R4 are selected from the group consisting of hydrogen and lower-alkyl, where R3 and R4 taken together with the adjacent nitrogen atom may form a heterocyclic ring selected from the group of piperidino, pyrrolidino, piperazino, and morpholino.