FENOTEROL HYDROBROMIDE Property

Melting point:

226-228°C

storage temp. 

2-8°C

solubility 

Soluble in water and in ethanol (96 per cent).

form 

Solid

color 

White to Off-White

Safety

Hazard Codes 

Xn

Risk Statements 

22

Safety Statements 

36

RIDADR 

3249

WGK Germany 

3

RTECS 

DO1500000

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

29225090

Toxicity

LD50 in mice (mg/kg): 1100 s.c.; 1990 orally (Goldenthal)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P501Dispose of contents/container to..…

FENOTEROL HYDROBROMIDE Chemical Properties,Usage,Production

in vivo

Fenoterol (0.7 mg/kg; intraperitoneal injection; twice a day; for 3 weeks) treatment suppresses mechanical allodynia during chronic treatment.

Chemical Properties

White Solid

Originator

Berotec,Boehringer Ingelheim,W. Germany,1972

Uses

An β2-adrenergic agonist. Bronchodilator; tocolytic.

Definition

ChEBI: The hydrobromide salt of fenoterol. A beta2-adrenergic agonist, it is used as a bronchodilator in the management of reversible airway obstruction.

Manufacturing Process

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- phenyl-2-(β-3',5'-diacetoxyphenyl-β-oxo)-ethyl-benzylamino-propane 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.

Therapeutic Function

Bronchodilator

Clinical Use

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).