42 results about "Amisulpride" patented technology

A benzamide derivative, especially amisulpride, is used to prevent or treat bipolar depression of a patient suffering from bipolar disorder I or bipolar disorder II.

The invention concretely relates to R-amisulpride medicine salt, a preparation method, a crystal form and application thereof in preparing a medicine for treating diabetes. The preparation method comprises the following steps: by adopting 2-aminomethyl-N-ethyl pyrrolidine as a raw material, and adopting L-tartaric acid, for splitting to obtain (R)-2-aminomethyl-N-ethyl pyrrolidine; directly condensing amisulpride acid and the (R)-2-aminomethyl-N-ethyl pyrrolidine under the catalysis of isopropyl chlorocarbonate and triethylamine, thus obtaining R-amisulpride; reacting the R-amisulpride obtained in the step (2) and acid to obtain the R-amisulpride medicine salt. The preparation method has the advantages of simplicity in operation, high safety, good product quality, low cost and the like, and is convenient for scale production.

Amisulpride is used in the therapy of nausea, vomiting or retches. The therapy may utilize a novel injectable formulation, in unit dosage form, comprising less than 50 mg amisulpride.

The invention relates to a synthesis method for amisulpride. The method comprises the following steps: a, esterifying 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid (I) and low alcohol (II) under the catalysis of thionyl chloride to obtain low alcohol ester (III), b, performing condensation on the low alcohol ester (III) obtained in the step a and N-ethyl-2-aminomethylpyrrolidine (IV) to obtain the amisulpride (V). The synthesis method is short in synthesis route (a target compound can be obtained by two steps), high in yield and atom utilization rate and easy to operate, reaction conditions are mild, a product purification post-treatment process is simple, the use of a catalyst harmful to the environment during the reaction is avoided, and a common recyclable solvent can be used as a reaction solvent.

The invention discloses a method for preparing a key intermediate of amisulpride. 2- methoxyl-4-amino-5-diethyl sulfide benzoic acid is oxidized in an alkaline condition so as to obtain the amisulpride acid (key intermediate of amisulpride). Compared with the existing methods, the method can produce products with higher quality, the yield is improved remarkably, the operation is simpler, safer, and has environment-friendly effect, and the method is especially suitable for industrial production.

The invention discloses an intermediate in amisulpride and a method for preparing amisulpride by using an intermediate. The method comprises the following steps: reacting 4-amino-2-methoxy group-5-ethylsulfonyl benzoic acid and di-tert-butyl dicarbonate ester so as to obtain the intermediate (4-(N-tert-tert-butoxycarbonyl)amino-2-methoxy group-5-ethylsulfonyl benzoic acid) of the amisulpride; and carrying out condensation reaction on the intermediate (4-(N-tert-butoxycarbonyl)amino-2-methoxy group-5-ethylsulfonyl benzoic acid) of the amisulpride and N-ethyl-2-aminomethyl pyrrolidine so as to obtain 4-(N-tert-tert-butoxycarbonyl)amino-N-((1-ethyl-2-pyrrolidyl)methyl)-5-ethylsulfonyl-2-methoxy benzamide, and carrying out deprotection of tert-butoxycarbonyl group (BOC) so as to obtain the amisulpride. According to the method, the process processing is simple, impurities which are hard to remove are avoided, the reaction yield is high and can be up to 76%, the purity of the obtained amisulpride is high, and the medical quality of the amisulpride is greatly improved.

The invention relates to a preparation method of amisulpride, which comprises the steps of carrying out condensation reaction on 4-amino-2-methoxy-5-ethyl sulfonyl methyl benzoate, N-ethyl-2-aminomethylpyrrolidine and a solvent at the temperature of 50-100 DEG C under the condition of taking organic alkali as a catalyst, and after the reaction is finished, concentrating the reaction liquid to remove the solvent, and filtering and drying to obtain the amisulpride. The organic alkali is sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, potassium tert-butoxide or sodium tert-butoxide, and the specific synthetic route is shown in the description. By adopting the preparation method disclosed by the invention, a catalyst harmful to the environment is not used in the reaction process, the post-treatment is simple, the solvent is a common recyclable solvent, the yield reaches 90% or above, the purity can reach 99.7%, the single impurity content is less than 0.1%, the requirements of medicinal preparations are met, and the preparation method is suitable for industrial production.

The invention provides a preparation method of amisulpride. The preparation method comprises the following steps: with 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid and thionyl chloride as raw materials, carrying out an acylation reaction to obtain 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride; and then, subjecting 2-methoxy-4-amino-5-ethylsulfonyl benzoyl chloride and N-ethyl-2-aminomethylpyrrolidine to an amidation reaction on to obtain amisulpride. The preparation method has the following advantages: raw materials are easy to obtain; highly toxic products are not used; the preparation method is simple; preparation period is short; side reactions are few; the yield and purity of the target product are high; and the target product has market competitiveness.

A fundamental shortcoming in the current treatment of schizophrenia is the lack of valid criteria to predict who will respond to antipsychotic treatment. The identification of blood-based biological markers of the therapeutic response would enable clinicians to identify the subgroup of patients in whom conventional antipsychotic treatment is ineffective and offer alternative treatments. As part of the Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) programme, the inventors conducted a transcriptome analysis on 188 subjects with first episode psychosis, all of whom were subsequently treated with amisulpride for 4 weeks. They identify 32 genes for which the expression changed after treatment in good responders only. Among these genes, the expression of ALPL, a gene involved in vitamin B6 metabolism, as well as CA4, DGTA2, DHRS13, HOMER3 and WLS showed a significant difference in expression level between good and poor responders before starting treatment, allowing to predict treatment outcome with a predictive value of 93.8% when combined with clinical features Collectively, these findings identified new mechanisms to explain symptom improvement after amisulpride medication and highlight the potential of combining gene-expression profiling with clinical data to predict treatment response in first episode psychoses.

Novel amisulpride derivatives and pharmaceutical compositions thereof are disclosed. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may have better membrane permeability compared to amisulpride. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for antagonizing dopamine and/or serotonin (e.g., 5-HT2a) and/or α2 receptor in a subject, either individually or in combination with other CNS active agents. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more conditions responsive to modulation of dopamine and/or serotonin (e.g., 5-HT2a) and/or α2 receptor in a subject, either individually or in combination with other CNS active agents. The amisulpride derivative disclosed herein or a pharmaceutical composition thereof may be used for treating one or more disorders associated with an abnormality in levels of dopamine and/or serotonin in the brain, either individually or in combination with other CNS active agents.