フルオキセチン塩酸塩 化学特性,用途語,生産方法
外観
白色～ほとんど白色, 結晶性粉末～粉末
溶解性
メタノール、エタノール、アセトニトリル、クロロホルム、アセトンに可溶。酢酸エチル、水、ジクロロメタンにわずかに可溶。[メタノール85 + 水15(体積比)]に溶ける。
用途
薬理・生理作用研究用。
効能
抗うつ薬, 選択的セロトニン再取り込み阻害薬
説明
Fluoxetine hydrochloride is a serotonin-selective antidepressant approved for the treatment of major depressive disorders, including those with concomitant anxiety.
It also appears effective in the treatment of obesity.
化学的特性
White to Off-White Powder
Originator
Lilly (USA)
使用
A labelled selective serotonin reuptake inhibitor (SSRI). Used as an antidepressant.
使用
A selective serotonin reuptake inhibitor (SSRI). Used as an antidepressant.
使用
A selectiive derotonin reuptake inhibitor. Used as an antidepressant
Manufacturing Process
About 600 g of β-dimethylaminopropiophenone hydrochloride were converted to the corresponding free base by the action of 1.5 N aqueous sodium hydroxide. Free base was dissolved in 2 L of THF, and the resulting solution added in dropwise fashion to a solution of 4 moles of diborane in 4 L of THF. The reaction mixture was stirred overnight. An additional mole of diborane in 1 L of THF was added, and the reaction mixture stirred again overnight. Next, 2 L of aqueous hydrochloric acid were added to decompose any excess diborane present. The tetrahydrofuran was removed by evaporation. The acidic solution was extracted twice with 1 L portions of benzene, and the benzene extracts were discarded. The acidic solution was then made basic with an excess of 5 N aqueous sodium hydroxide. The basic solution was extracted three times with 2 L portions of benzene. The combined extracts washed with a saturated aqueous sodium chloride and then dried. Evaporation of the solvent in vacuo yields 442 g of N,N-dimethyl-3-phenyl-3hydroxypropylamine.
A solution containing 442 g of N,N-dimethyl-3-phenyl-3-hydroxypropylamine in 5 L of chloroform was saturated with dry gaseous hydrogen chloride. 400 mL of thionyl chloride were then added to the solution at a rate sufficient to maintain reflux. The solution was refluxed an additional 5 hours. Evaporation of the chloroform and other volatile constituents in vacuo yielded N,Ndimethyl-3-phenyl-3-chloropropylamine hydrochloride which was collected by filtration, and the filter cake washed twice with 1.5 L portions of acetone. The washed crystals weighed about 500 g and melted at 181-183°C with decomposition. An additional 30 g of compound were obtained from the acetone wash by standard crystallization procedures. The structure of the above compound was verified by NMR and titration.
A solution of 50 g p-trifluoromethylphenol, 12 g of solid sodium hydroxide and 400 mL of methanol were added 29.8 g of N,N-dimethyl 3-phenyl-3chloropropylamine hydrochloride. The resulting reaction mixture was refluxed for about 5 days and then cooled. The methanol was removed by evaporation, and the resulting residue taken up in a mixture of ether and 5 N aqueous sodium hydroxide. The ether layer was separated and washed twice with 5 N aqueous sodium hydroxide and three times with water. The ether layer was dried, and the ether removed by evaporation in vacuo to yield as a residue N,N-dimethyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine.
To a solution 8.1 g of cyanogen bromide in 500 mL benzene and 50 mL of toluene at 5°C in nitrogen was added dropwise a solution of 12.146 g of N,Ndimethyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine in 40 mL of benzene. The temperature of the reaction mixture was allowed to rise slowly to room temperature, at which temperature stirring was continued overnight while still maintaining a nitrogen atmosphere. 100 mL of benzene were added. The reaction mixture was washed twice with water, once with 2 N aqueous sulfuric acid and then with water until neutral. The organic layer was dried, and the solvents removed therefrom by evaporation in vacuo to yield about 9.5 g of an oil comprising N-methyl-N-cyano-3-(p-trifluoromethylphenoxy)-3phenylpropylamine.
The reaction mixture containing 100 g potassium hydroxide, 85 mL water, 400 mL ethylene glycol and 9.50 g of N-methyl-N-cyano-3-(ptrifluoromethylphenoxy)-3-phenylpropylamine was heated to refluxing temperature for 20 hours, and was then cooled. 500 mL of water were added. The reaction mixture was extracted with three 500 mL portions of ether. The combined extracts washed with water. The water wash was discarded. The ether solution was next contacted with 2 N aqueous hydrochloric acid. The acidic aqueous layer was separated. A second aqueous acidic extract with 2 N hydrochloric acid was made followed by three aqueous extracts and an extract with saturated aqueous sodium chloride. The aqueous layers were all combined and made basic with 5 N aqueous sodium hydroxide. N-methyl 3(p-trifluoromethylphenoxy)-3-phenylpropylamine, formed in the above reaction, was insoluble in the basic solution and separated. The amine was extracted into ether. Two further ether extractions were carried out. The ether extracts were combined, and the combined extracts washed with saturated aqueous sodium chloride and then dried. Evaporation of the ether in vacuo yielded about 6.3 g of N-methyl-3-(p-trifluoromethylphenoxy)-3phenylpropylamine. The amine free base was converted to the corresponding hydrochloride salt.
brand name
Prozac (Lilly); Sarafem (Lilly); Sarafem (Warner Chilcott).
Therapeutic Function
Antidepressant
生物活性
Selective serotonin reuptake inhibitor. Binds to the human 5-HT transporter with a K i of 0.9 nmol/l and is between 150- and 900- fold selective over 5-HT 1A , 5-HT 2A , H 1 , α 1 , α 2 -adrenergic, and muscarinic receptors. Antidepressant. Also available as part of the Serotonin Uptake Inhibitor Tocriset™ .
フルオキセチン塩酸塩 上流と下流の製品情報
原材料
準備製品
