- Novel preparation method of azasetron hydrochloride
-
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 method for synthesizing arab League grips Si Qiong hydrochloric acid
-
The invention relates to new path azasetron hydrochloride, and belongs to the technical field of medicine. The method comprises the steps of taking 6-chlorine-4-methyl-3-keto-3,4-dihydro-2H-1,4-benzoxazine-8-methyl formate as a raw starting material, hydrolyzing into 6-chlorine-4-methyl-3-keto-3,4-dihydro-2H-1,4-benzoxazine-8-formic acid in an alcohol-alkali aqueous solution, activating carboxylic acid with TBTU (O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate), condensing with 3-aminoquinuclidine dihydrochloride directly, and finally salifying with concentrated hydrochloric acid to prepare azasetron hydrochloride. According to the method, TBTU serves as a condensing reagent, so that the reaction steps are simplified, pollution to an environment and equipment is reduced, aftertreatment is more convenient, later purification is easier, and industrial production of a product is facilitated further.
- -
-
Paragraph 0015; 0030; 0031
(2017/02/09)
-
- Use of serotonin antagonists for treating fibromyalgia
-
The invention is directed to the use of 5HT3 antagonists of formula I STR1 wherein the substituents are as defined herein.
- -
-
-
- Synthesis and pharmacology of 3,4-dihydro-3-oxo-1,4-benzoxazine-8-carboxamide derivatives, a new class of potent serotonin-3 (5-HT3) receptor antagonists
-
A series of 3,4-dihydro-3-oxo-1,4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity assessed by their ability to antagonize the von Bezold-Jarish (BJ) effect in rats. Derivatives bearing 1-azabicyclo[2.2.2]oct-3-yl moiety as a basic function attached to the carboxamide at position 8 showed more potent antagonistic activity than those bearing the other three basic moieties. Structure activity relationships of this series showed that methyl and chloro groups were more effective as substituents at positions 4 and 6, respectively. The representative compound 15 (Y-25130) in this series showed potent antagonistic activity on the BJ effect (ED50 = 1.3 μg/kg i.v.), high affinity for 5-HT3 receptor (K(i) = 2.9 nM) and complete protection against cisplatin-induced emesis in dogs at a dose of 0.1 mg/kg i.v.
- Kawakita,Kuroita,Yasumoto,Sano,Inaba,Fukuda,Tahara
-
p. 624 - 630
(2007/10/02)
-
