Sibutramine

Sibutramine Chemische Eigenschaften,Einsatz,Produktion Methoden

• Originator

  Meridia,Abbott Laboratories,USA

• Verwenden

  Anorexic; antidepressant.

• Definition

  ChEBI: A tertiary amino compound that is N,N,3-trimethylbutan-1-amine substituted by a (4-chlorophenyl)cyclobutyl group at position 1.

• Manufacturing Process

  A solution of 4-chlorobenzyl cyanide and 1,3-dibromopropane in dry dimethylsulfoxide was added dropwise under nitrogen to a stirred mixture of sodium hydride dispersed in mineral oil and dimethylsulfoxide at a temperature in the range 30° to 35°C. The mixture was stirred at room temperature for 2 h and propan-2-ol and then water were added dropwise. The mixture was filtered through a diatomaceous earth sold under the Registered Trade Mark CELITE and the solid residue washed with ether. The ether layer was separated, washed with water, dried and evaporated. 1-(4- Chlorophenyl)-1-cyclobutanecarbonitrile was isolated by distillation.
  1-(4-Chlorophenyl)-1-cyclobutanecarbonitrile (37.6 g) was added to a solution of potassium hydroxide (32.4 g) in diethyleneglycol (370 ml) and the mixture heated under reflux for three and a 0.5 h The reaction mixture was poured into an ice/water mixture and the resulting solution was washed with ether. The aqueous layer was added to a mixture of concentrated hydrochloric acid (100 ml) and ice and the resulting precipitate of 1-(4-chlorophenyl)-1- cyclobutanecarboxylic acid (melting point 86°-88°C) collected, washed with water and dried.
  1-(4-Chlorophenyl)-1-cyclobutane carboxylic acid (10.5 g) was heated under reflux with thionyl chloride (20 ml) for 2.5 h. Excess thionyl chloride was evaporated off and the acid chloride of the above acid distilled (boiling point 82°-96°C /0.2 mm Hg). A solution of the acid chloride in dry tetrahydrofuran was added slowly to the product of the reaction of magnesium turnings and ethyl bromide in dry tetrahydrofuran. Water was added followed by 5 N hydrochloric acid with cooling. The reaction mixture was extracted with ether, washed with water, sodium bicarbonate solution, dried. The solvent was removed by evaporation and 1-isobutyl-1-(4-chlorophenyl)cyclobutane obtained by distillation. The 1-isobutyl-1-(4-chlorophenyl)cyclobutane, diethylene glycoldimethyl ether, water and concentrated hydrochloric acid were mixed and heated under reflux. The mixture was poured into water aqueous NaOH was added and the product extracted into ether. Evaporation gave a dark oil. A sample of this oil, water and formic acid were mixed and formaldehyde added. The mixture was heated under reflux and then concentrated hydrochloric acid and propan-2-ol were added. Evaporation to dryness gave N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]isobutyl hydrochloride as a white solid.

• Trademarks

  Meridia (Abbott).

• Therapeutic Function

  Antidepressant, Anorexic

• Allgemeine Beschreibung

  Sibutramine (Meridia) is said to be an uptake inhibitor ofNE and 5-HT. These mechanisms fit its structure. It is reportedlyan antidepressant and an anorexiant drug. Thismechanism implies that activation of all presynaptic andpostsynaptic receptors in NE and 5-HT systems is possible.The data are not completely clear, but studies to date indicatethat the receptors principally involved are α1, β1, and5-HT_2C.

Sibutramine Upstream-Materialien And Downstream Produkte

106650-56-0, Sibutramine Verwandte Suche: