23031-25-6 Usage
Description
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol is a phenylethanolamine derivative with a catechol substitution at the 5th position by a 2-(tert-butylamino)-1-hydroxyethyl group. It is structurally related to terbutaline, a synthetic congener of adrenaline that acts as a bronchodilator and tocolytic agent.
Uses
Used in Pharmaceutical Industry:
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol is used as an active pharmaceutical ingredient for the development of bronchodilators and tocolytics due to its structural similarity with terbutaline, which is a known β2-adrenergic receptor agonist.
Used in Research and Development:
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol is used as a research tool for studying the effects of β2-adrenergic receptor agonists on various physiological processes, including bronchodilation, tocolysis, and potential applications in treating certain neuromuscular disorders.
Used in Drug Delivery Systems:
Similar to terbutaline, 5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol may be utilized in the development of novel drug delivery systems to enhance its bioavailability and therapeutic outcomes in various medical applications.
Used in Asthma Treatment:
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol is used as a bronchodilator for preventing and relieving bronchospasms in bronchial asthma, chronic bronchitis, pulmonary emphysema, and other broncho-pulmonary diseases, given its structural resemblance to terbutaline, which has been used in the treatment of asthma.
Used in Premature Labor Prevention:
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol may be used for the prevention of premature labor, as it shares structural and functional similarities with terbutaline, which has been used for this purpose. However,
Originator
Bricanyl,Pharma-Stern,W. Germany,1971
Indications
Terbutaline (Brethine, Bricanyl) is a relatively specific
β2-adrenoceptor agonist.
Terbutaline can prevent premature labor, especially in
individuals who are more than 20 weeks into gestation
and have no indication of ruptured fetal membranes or
in whom labor is not far advanced. Its effectiveness in
premature labor after 33 weeks of gestation is much less
clear. Terbutaline can decrease the frequency, intensity,
and duration of uterine contractions through its ability
to directly stimulate β2-adrenoceptors. While it appears
to be especially selective for β2-receptor activation,
terbutaline does have some β1 activity as well.
Manufacturing Process
To a solution of 32 g of benzyl-t-butylamine in 300 ml of absolute ethanol at
reflux temperature was added 32 g of 3,5-dibenzyloxy-?-bromoacetophenone
in 10 ml of dry benzene. The mixture was refluxed for 20 hours and then
evaporated. When absolute ether was added to the residue, benzyl-tbutylamine
hydrobromide was precipitated. The precipitated compound was
filtered off and to the filtrate was added an excess of 2 N sulfuric acid. This
caused precipitation of the hydrogen sulfate of 3,5-dibenzyloxy-?-(benzyl-tbutylamino)-
acetophenone which was recrystallized from acetone/ether. If the product is crystallized from different organic solvents, the melting point will
vary with the type and amount of solvent of crystallization, but the product
can be used directly for hydrogenation. 15 g of 3,5-dibenzyloxy-?-(benzyl-t-butylamino)-acetophenone hydrogen
sulfate in 200 ml of glacial acetic acid were hydrogenated in a Parr pressure
reaction apparatus in the presence of 1.5 g of 10% palladium charcoal at
50°C and 5 atmospheres pressure. The reaction time was 5 hours. The
catalyst was filtered off, the filtrate was evaporated to dryness and the
hydrogen sulfate of 1-(3',5'-dihydroxyphenyl)-2-(t-butylamino)-ethanol was
received. This compound is hygroscopic, but it can be transformed into a
nonhygroscopic sulfate in the following manner.The hydrogen sulfate was dissolved in water and the pH of the solution was
adjusted to 5.6 (pH-meter) with 0.1 N sodium hydroxide solution. The water
solution was evaporated to dryness and the residue dried with absolute
ethanol/benzene and once more evaporated to dryness. The remaining crystal
mixture was extracted in a Soxhlet extraction apparatus with absolute
methanol. From the methanol phase the sulfate of 1-(3',5'-dihydroxyphenyl)-
2-(t-butylamino)-ethanol crystallized. Melting point 246°C to 248°C.
Therapeutic Function
Bronchodilator
Mechanism of action
Terbutaline is a synthetic sympathomimetic amine. It is one of the most selective direct–acting
stimulants of β2-adrenoreceptors. It stimulates smooth muscle β2-adrenoreceptors in the
bronchi, relaxing them and relatively minutely acting on the β1—receptors of the heart.
Clinical Use
Terbutaline should be initially used only in an
appropriate hospital setting where any obstetric complications
can be readily addressed. After initial administration,
it can be used in the outpatient setting.
Concomitant use of β2-adrenergic agonists and corticosteroids
have additional diabetic effects and may
rarely lead to pulmonary edema.The combination of β2-
adrenergic agonists and magnesium sulfate can cause
cardiac disturbances, while coadministration of terbutaline
with other sympathomimetics can lead to the potentiation
of the actions of the latter drugs.
Side effects
Terbutaline is frequently used in the management of
premature labor, although it has not been marketed for
such use. Its effectiveness, side effects, precautions, and
contraindications are similar to those of all β2-adrenergic
agonists. Terbutaline can cause tachycardia, hypotension,
hyperglycemia, and hypokalemia. It can be
given orally in addition to subcutaneous or intravenous
administration.
Synthesis
Terbutaline, α-[(tert-butylamino)methyl]-3,5-dihydroxybenzylic alcohol
(11.1.14), differs from the examined compounds mainly in the location of hydroxyl
groups in the benzene ring, and is synthesized by brominating 3,5-dibenzyloxyαcetophenone into the appropriate 3,5-dibenzyloxybromoacetophenone (11.1.12), which is
reacted with N-benzyl-N-tert-butylamine, giving the aminoketone (11.1.13). Reduction
of this product by hydrogen over a palladium catalyst leads to terbutaline (11.1.14)
[16–18].
Environmental Fate
Terbutaline is administered as the sulfate. It is a white to graywhite,
crystalline powder; nearly odorless or with the faint odor
of acetic acid. Terbutaline has a slightly bitter taste. It has
a melting point of 247°C. Terbutaline sulfate is soluble at 1 g
per 1.5 ml water or 250 ml of ethanol. It is soluble in 0.1 N
hydrochloric acid, slightly soluble in methanol, and insoluble
in chloroform. While terbutaline is stable under normal
conditions as a solid, it is unstable in light. Terbutaline is
degraded through oxidative processes; this is enhanced in the
presence of trace levels of metals and in the presence of oxygen.
No information is currently available on breakdown in soil,
groundwater, or surface water.
Toxicity evaluation
The primary mechanism of terbutaline is the stimulation of
adenyl cyclase, which catalyzes cyclic adenosine monophosphate
(AMP) from adenosine triphosphate (ATP). In the
liver, buildup of cyclic AMP stimulates glycogenolysis and an
increase in serum glucose. In skeletal muscle, this process
results in increased lactate production. Direct stimulus of
sodium/potassium ATPase in skeletal muscle produces a shift
of potassium from the extracellular space to the intracellular
space. Relaxation of smooth muscle produces a dilation of the
vasculature supplying skeletal muscle, which results in a drop
in diastolic and mean arterial pressure (MAP). Terbutaline has
greater b2 selectivity, but overdose will have both β1 and β2
activity. Tachycardia occurs as a reflex to the drop in MAP or as
a result of β1 stimulus. β1-Adrenergic receptors in the locus
ceruleus also regulate norepinephrine-induced inhibitory
effects, resulting in agitation, restlessness, and tremor.
Check Digit Verification of cas no
The CAS Registry Mumber 23031-25-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,3,0,3 and 1 respectively; the second part has 2 digits, 2 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 23031-25:
(7*2)+(6*3)+(5*0)+(4*3)+(3*1)+(2*2)+(1*5)=56
56 % 10 = 6
So 23031-25-6 is a valid CAS Registry Number.
InChI:InChI=1/C21H25N.ClH/c1-21(2,3)15-8-5-9-16-22(4)17-19-13-10-12-18-11-6-7-14-20(18)19;/h5-7,9-14H,16-17H2,1-4H3;1H/b9-5+;
23031-25-6Relevant articles and documents
Enantioselective resolution of Rac-terbutaline and evaluation of optically pure R-terbutaline hydrochloride as an efficient anti-asthmatic drug
Beng, Huimin,Zhang, Hao,Jayachandra,Li, Junxiao,Wu, Jie,Tan, Wen
, p. 759 - 768 (2018)
Terbutaline is a β2-adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R-isomer was found to be the potent enantiomer in generating therapeutic effect, while S-isomer has been reported to show side effects. In this study, R-terbutaline hydrochloride (R-TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac-TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R-TBH 6 nebulized solution was prepared in half dosage of Bricanyl, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti-asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R-TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti-asthmatic effect with Bricanyl.
Preparation method of terbutaline
-
Paragraph 0038; 0042-0043, (2020/12/05)
The invention belongs to the field of pharmacy, and particularly relates to a preparation method of terbutaline. The method comprises: S1, adding a compound I and dichloromethane into a reaction kettle, stirring and dissolving, and then adding anhydride, S2, after the reaction is finished, adding dilute alkaline water into the system, fully stirring and washing, collecting a dichloromethane phase,and carrying out reduced pressure distillation to obtain a yellow oily matter, namely a compound II, S3, adding the compound II, ethyl acetate, tert-butylamine, sodium hydroxide and an oxidation protective agent into the reaction kettle, and S4, after the reaction in the step S3 is finished, adding purified water into the system to wash the reaction solution in the step S3, collecting an ethyl acetate phase, and carrying out reduced pressure distillation on the ethyl acetate phase to obtain terbutaline. According to the technical scheme provided by the invention, the post-reaction treatment difficulty is reduced, so that an intermediate compound is easily separated from a reaction system, meanwhile, side reactions such as epoxy bond hydrolysis are avoided, and the stability and yield of the final product terbutaline are improved.
Preparation method of terbutaline sulfate
-
Paragraph 0017; 0029; 0032; 0034; 0037; 0039; 0042; 0044, (2020/04/29)
The invention discloses a preparation method of terbutaline sulfate, wherein the method comprises the following steps: carrying out a bromination reaction on 3,5-dihydroxyacetophenone as a raw material by using a bromination reagent without hydroxyl protection, carrying out reduction and ring closing, carrying out a ring-opening reaction with tert-butylamine, and finally forming a salt with sulfuric acid to obtain terbutaline sulfate. According to the method, the defects of requirement of deprotection after hydroxyl protection, use of various high-risk highly toxic reagents, long reaction stepand low yield in the prior art are overcome.
