Brominated crebanine compound and preparation method and application thereof
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A technology of bromocribanine and compound, applied in the field of medicine, can solve the problems of hypothyroidism or hyperthyroidism, lung damage, difficulty in finding antiarrhythmic drugs, adverse reactions and the like
Active Publication Date: 2017-02-08
YUNNAN UNIV OF TRADITIONAL CHINESE MEDICINE
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The reports about the antiarrhythmic effect of 3-bromocarbanine and 10,11-bromocarbanine have not been reported before the completion of the present invention
[0005] 3-Bromocrebanine (3-Bromocrebanine) and 10,11-Bromocrebanine (10,11-Dibromocrebanine) are synthesized from Crebanine (Crebanine). see related reports
[0006] Most commonly used antiarrhythmic drugs on the market are accompanied by adverse reactions that cannot be ignored. For example, lidocaine often manifests as dizziness, paresthesia, con
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[0084] Preparation method embodiment 1
[0085] Step (1), under ice bath conditions, add trifluoroacetic acid to the crobanin to completely dissolve the crobanin; then slowly add N-bromosuccinimide, N-bromosuccinimide The addition time of O is more than 10 minutes; after the addition, the ice bath is removed, the reaction solution is placed at room temperature and stirred for 11 hours, and then the solvent is evaporated to remove trifluoroacetic acid to obtain a concentrate;
[0086] The mass-volume ratio of crobanin to trifluoroacetic acid is 0.2:4.9; the molar ratio of crobanin to N-bromosuccinimide is 1:1.1;
[0087] Step (2), add water 9.5 times the volume of trifluoroacetic acid to the concentrate obtained in step (1), and then use saturated Na 2 CO 3 Adjust the pH of the aqueous solution to 8, then use CH 2 Cl 2 Perform extraction, extract 2 times, extract CH each time 2 Cl 2 The usage amount is one-fifth of the volume of water, and the organic layers are combined;
[0088] Step...
Example Embodiment
[0113] Example 2
[0114] An antiarrhythmic drug, comprising the following components in parts by weight: 250 parts of bromocobanin compounds, 60 parts of icing sugar, and 5 parts of dextrin; the bromocobanin compounds are 3 -Bromocrabanine or 10,11-bromocrabanine and pharmaceutically acceptable salts thereof. The bromocribanin compound is 10,11-bromocribanin.
[0115] The preparation method is the same as in Example 1.
Example Embodiment
[0116] Example 3
[0117] An anti-arrhythmic drug, comprising the following components in parts by weight: 120 parts of bromocobanin compounds, 90 parts of icing sugar, and 10 parts of dextrin; the bromocobanin compounds are 3 -Bromocrabanine or 10,11-bromocrabanine and pharmaceutically acceptable salts thereof.
[0118] The bromocobanin compound is a pharmaceutically acceptable salt of 3-bromocobanin.
[0119] The preparation method is the same as in Example 1.
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Abstract
The invention relates to a brominated crebanine compound and preparation method and an application thereof, which belongs to the technical field of medicine. The invention firstly discloses the synthesis of 3-brominated crebanine and 10, 11-brominated crebanine, through research on effect of chloroform for inducing mice arrhythmia, the research shows that the 3-brominated crebanine and 10, 11-brominated crebanine can antagonize the chloroform-induced ventricular fibrillation, so that the 3-brominated crebanine and 10, 11-brominated crebanine have anti-arrhythmia effect through preliminary determination; the barium chloride-induced rat ventricular rhythm tests confirm that the 3-brominated crebanine and 10, 11-brominated crebanine have good anti-arrhythmia effect, acute toxicity of two brominated crebanine compounds is lower than that of crebanine, LD50 is 65.15+/-1.132 mg/kg of 3-brominated crebanine and 59.62+/-2.610 mg/kg of 10,11-brominated crebanine respectively, and a good base can be established for further deep researches.
Description
technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to bromocarbanine compounds and their preparation methods and applications. Background technique [0002] Cardiac arrhythmia refers to abnormalities in the frequency, rhythm, origin, conduction velocity, or sequence of cardiac impulses. Arrhythmia is an important group of diseases in cardiovascular diseases. It can occur alone or accompany other cardiovascular diseases. Its prognosis is related to the etiology, inducement, evolution trend of arrhythmia, and whether it leads to severe hemodynamic disturbance. It can occur suddenly and cause sudden death, or it can continue to involve the heart and cause it to fail. Although there are radiofrequency ablation and other treatment methods, antiarrhythmic drugs are still the main treatment method or an essential part of it. For a long time, people have been unremittingly committed to the research and development of antiarrhy...
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