123040-16-4 Usage
Description
Azasetron hydrochloride, also known as Nazasetron, is a potent 5-HT3 receptor antagonist that is used in the medical field for the prevention and treatment of severe nausea and vomiting. It is the fourth in its class to reach the market and is particularly effective in cases induced by cytotoxic chemotherapy and total body X-radiation. Azasetron hydrochloride is a white to off-white solid and is marketed under the brand name Serotone. It is unique in that it does not possess dopamine D2 receptor blocking activity, which means it is free of the extrapyrimidal side effects associated with other commonly used antiemetics.
Uses
Used in Oncology:
Azasetron hydrochloride is used as an antiemetic agent for the management of nausea and vomiting induced by cancer chemotherapy. It is a selective 5-HT3 receptor antagonist with an IC50 of 0.33 nM, making it highly effective in this application.
Used in Gastroenterology:
Azasetron hydrochloride is used as a treatment option for gastrointestinal motility dysfunctions such as gastric stasis, vomiting, and irritable bowel syndrome. Its effectiveness in these areas has been reported in various studies, showcasing its potential usefulness in treating these conditions.
Used in Radiation Therapy:
In addition to its use in chemotherapy-induced emesis, Azasetron hydrochloride is also utilized in the prevention of severe nausea and vomiting caused by total body X-radiation. Its potent 5-HT3 receptor antagonist properties make it a valuable asset in this context.
Overall, Azasetron hydrochloride is a versatile and effective pharmaceutical compound with applications in various medical fields, particularly in oncology and gastroenterology. Its unique properties and lack of certain side effects make it a preferred choice for many patients and healthcare professionals.
Originator
Yoshitomi (Japan)
Manufacturing Process
To a solution of 2-(2-carboxy-4-chlorophenoxy)acetic acid in concentrated
sulfuric acid is added dropwise a mixed liquid of fuming nitric acid and
concentrated sulfuric acid under stirring with keeping at a temperature below
10°C. After the addition, the reaction mixture is stirred and poured into 10 L
of ice-cold water. The precipitated crystals are collected by filtration, washed
with 2 L of water four times and them dried to give 2-(2-carboxy-4-chloro-6-
nitrophenoxy)acetic acid.
To a solution of ferrous sulfate heptahydrate in of hot water is added a
solution of 2-(2-carboxy-4-chloro-6-nitrophenoxy)acetic acid and aqueous
concentrated ammonia solution in water under stirring. After stirring, to the
reaction mixture is twice added aqueous concentrated ammonia solution.
While the reaction mixture becomes exothermic, stirring is continued. The
resultant mixture is filtered through a celite layer under reduced pressure and
washed with hot water twice. The filtrate is cooled and made acid with
concentrated hydrochloric acid. The precipitated crystals are washed with
water and dried to give 6-chloro-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-
carboxylic acid.
A mixture of 6-chloro-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxylic
acid, methanol and concentrated sulfuric acid is refluxed under heating with
stirring, and then cooled. The precipitated crystals are collected by filtration,
washed with methanol and dried to give methyl 6-chloro-3,4-dihydro-3-oxo-
2H-1,4-benzoxazine-8-carboxylate, melting point 239°-241°C.
To a solution of methyl 6-chloro-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxylate in dimethylformamide is added potassium t-butoxide and solution
stirred at room temperature. To the resultant solution is added dropwise a
solution of methyl iodide in dimethylformainide under stirring. After the
reaction solution is stirred, water is added thereto. The insoluble substance is
collected by filtration, washed with water and dried to give methyl 6-chloro-
3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxylate.
A mixture of methyl 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-1,4-
benzoxazine-8-carboxylate, ethanol and 4% aqueous potassium hydroxide
solution is refluxed with heating. The resultant solution is cooled and water is
added thereto followed by filtration. The filtrate is made acid with
concentrated hydrochloric acid. The precipitated crystals are collected by
filtration, washed with water and dried, and then recrystallized from ethanol
to give 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxylic
acid, melting point 241°-243°C.
A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-
carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below
0°C and triethylamine is added under stirring thereto. Further, ethyl
chlorocarbonate is added and the mixture is stirred at room temperature. To
the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the
mixture stirred. After completion of the reaction, aqueous sodium hydrogen
carbonate and ethyl acetate are added. The organic layer is separated,
washed with water and dried over magnesium sulfate. The solvent is distilled
off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-
oxo-2H-1,4-benzoxazine-8-carboxamide.
In practice it is usually used as hydrochloride.
Therapeutic Function
Antiemetic
Biological Activity
A selective and potent 5-HT 3 antagonist (K i = 2.9 nM).
Check Digit Verification of cas no
The CAS Registry Mumber 123040-16-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,3,0,4 and 0 respectively; the second part has 2 digits, 1 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 123040-16:
(8*1)+(7*2)+(6*3)+(5*0)+(4*4)+(3*0)+(2*1)+(1*6)=64
64 % 10 = 4
So 123040-16-4 is a valid CAS Registry Number.
InChI:InChI=1/C17H20ClN3O3.ClH/c1-20-14-7-11(18)6-12(16(14)24-9-15(20)22)17(23)19-13-8-21-4-2-10(13)3-5-21;/h6-7,10,13H,2-5,8-9H2,1H3,(H,19,23);1H
123040-16-4Relevant articles and documents
Novel preparation method of azasetron hydrochloride
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, (2019/12/25)
The invention provides a novel preparation method of azasetron hydrochloride, belonging to the technical field of medicine synthesis. According to the method, methyl 5-chlorosalicylate is used as a raw material; after acetic anhydride nitrification and stannous chloride reduction at room temperature, dimethyl carbonate is used as a methylation reagent, and an intermediate V (6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxylic acid methyl ester) is synthesized by adopting a one-pot method; the intermediate V is hydrolyzed to obtain 6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-formic acid (VI); and the compound reacts with free 3-aminoquinuclidine dihydrochloride for 1 h under the catalysis of TBTU to form a salt so as to obtain I (azasetron hydrochloride). According to the method, the yield of each step is high; aftertreatment is simple; the reaction time of each step is short; conditions are mild; low-toxicity environment-friendly reagents are adopted; energy consumption is reduced; cost is saved; and industrial production is better facilitated.
A hydrochloric acid arab League grips Si Qiong method for the preparation of
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Paragraph 0015; 0016; 0089, (2016/12/01)
The invention discloses a method for preparing azasetron hydrochloride. The method comprises the following steps: hydrolyzing 6-chloro-4-methyl-3-oxo-3,4- dihydro-2H-1,4-benzoxazine-8-carboxylic acid methyl ester which serves as an initial material to prepare carboxylic acid; condensing with 2,2'-dibenzothiazyl disulfide under the action of triethylamine and triethyl phosphite to prepare active ester of carboxyl-2-benzothiazolyl thioester; directly condensing with a 3-aminoquinuclidine alkaline aqueous solution without separation, and salifying to prepare the azasetron hydrochloride. The method can be used for avoiding multiple steps of reaction and pollution to environment, has mild reaction condition and relatively high yield, and is suitable for industrialization.
