- Product Name:
- FENOTEROL HYDROBROMIDE
- FENOTEROL HBR
- FENOTEROL HYDROBROMIDE
- 2-[3,5-DIHYDROXYPHENYL]-2-HYDROXY-2'-[4-HYDROXYPHENYL]-1'-METHYLDIETHYLAMINE HYDROBROMIDE
- Product Categories:
- Intermediates & Fine Chemicals
- Mol File:
FENOTEROL HYDROBROMIDE Chemical Properties
- Melting point:
- storage temp.
- Soluble in water and in ethanol (96 per cent).
- Language:English Provider:SigmaAldrich
FENOTEROL HYDROBROMIDE Usage And Synthesis
Berotec,Boehringer Ingelheim,W. Germany,1972
An β2-adrenergic agonist. Bronchodilator; tocolytic.
ChEBI: The hydrobromide salt of fenoterol. A beta2-adrenergic agonist, it is used as a bronchodilator in the management of reversible airway obstruction.
441 grams (1.4 mols) of 3,5-diacetoxy-α-bromo-acetophenone (MP 66°C),
prepared by bromination of 3,5-diacetoxy-acetophenone, were added to a
solution of 714 grams (2.8 mols) of 1-p-methoxyphenyl-2-benzylaminopropane
in 1,000 cc of benzene, and the resulting solution mixture was
refluxed for 1 hour. The molar excess of 1-p-methoxy-phenyl-2-benzylaminopropane
precipitated out as its hydrobromide. After separation of the
precipitated hydrobromide of the amino component, the hydrochloride of 1-pmethoxy-
was precipitated from the reaction solution by addition of an ethanolic solution
of hydrochloric acid. The precipitate was separated and, without further
purification, was deacetylated by boiling it in a mixture of 2 liters of aqueous
10% hydrochloric acid and 1.5 liters of methanol.
The resulting solution was filtered through animal charcoal and, after addition of 2 liters of methanol, it was debenzylated by hydrogenation at 60°C over palladinized charcoal as a catalyst. After removal of the catalyst by filtration, the filtrate was concentrated by evaporation, whereupon the hydrochloride of 1-p-methoxyphenyl-2-(β-3',5'-dihydroxyphenyl-β-oxo)-ethylamino-propane (MP 244°C) crystallized out. For the purpose of demethylation, the 350 grams of the hydrochloride thus produced were refluxed for 2 hours with 3.5 liters of aqueous 48% hydrobromic acid. Upon cooling of the reaction solution, 320 grams of 1-p-hydroxyphenyl-2-(β-3',5'-dihydroxyphenyl-β-oxo)-ethylaminopropanehydrobromide (MP 220°C) crystallized out.
·220 grams of 1-p-hydroxyphenyl-2-(β-3',5'-dihydroxyphenyl-β-oxo)- ethylamino-propane hydrobromide were dissolved in 1 liter of methanol, the resulting solution was boiled with activated charcoal, the charcoal was filtered off and the filtrate was hydrogenated in the presence of Raney nickel at 60°C and 5 atmospheres gauge. Thereafter, the catalyst was filtered off, the methanolic solution was admixed with a small amount of concentrated hydrobromic acid, and the mixture was evaporated to dryness in vacuo. The residue was stirred with acetone, the mixture was vacuum filtered and the filter cake was recrystallized from a mixture of methanol and ether. The 1-phydroxyphenyl- 2-(β-3',5'-dihydroxyphenyl-β-hydroxy)-ethylamino-propane hydrobromide thus obtained had a melting point of 222° to 223°C.
Fenoterol is an investigational drug in the United States that has been in use in Europe since 1970. It is the p-hydroxyphenyl derivative of metaproteronol, and the combination of the resorcinol ring and the bulky p-hydroxyphenyl isopropyl group on the nitrogen gives fenoterol significant β2-receptor selectivity. It has approximately half the affinity for the β2-receptor as compared to albuterol. The resorcinol ring is resistant to COMT metabolism, and the bulky nitrogen substituent greatly retards MOA metabolism as well giving fenoterol a reasonable oral bioavailability with pharmacokinetics similar to albuterol (i.e., rapid onset and a 4- to 6-hour duration of action after oral inhalation).
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