33 results about "Bedaquiline" patented technology

The invention discloses an intermediate for preparing bedaquiline and a preparation method therefor. The intermediate disclosed by the invention has the advantages that the intermediate avoids hydrogenation and enolization of an alpha-site in the intermediate, reduces occurrence of side reactions, and increases the conversion rate of raw materials and the total yield of reaction, and is suitable for large-scale industrial production. The intermediate for preparing bedaquiline is characterized by being a compound with a structural formula (9) or an optical isomer thereof: FORMULA is shown in the description.

The invention relates to a method for recycling and utilizing Bedaquiline stereochemical isomers. The isomers comprise (alpha R, beta R), (alpha S, beta S), and (alpha R, beta S)-6-bromine-alpha-[2-(dimethyl amidogen) ethyl]-2-methoxy-alpha-1-naphthyl-beta-phenyl-3-quinoline ethanol. The recycled isomers can generate X and Y with the high conversion rate, and X and Y can be used for synthesizing Bedaquiline again. According to the process method, the production cost of the Bedaquiline can be greatly lowered, and the utilization rate of raw materials can be improved. See the formula in the specification.

This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the anti-TB compound bedaquiline, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of a pathogenic mycobacterial infection.

The present invention relates to a combination of bedaquiline, a macrolide (e.g. clarithromycin) and, optionally, ethambutol for use in the treatment of a disease associated with nontuberculous mycobacteria (NTM).

The present invention relates to a combination of bedaquiline, a macrolide (e.g. clarithromycin) and, optionally, ethambutol for use in the treatment of a disease associated with nontuberculous mycobacteria (NTM).

The invention provides application of a compound, an antibacterial composition and application of the antibacterial composition and relates to the technical field of medicinal chemical industry. The compound is a compound X9, and the antibacterial composition is prepared from the compound X9 and an antituberculosis drug. According to the compound X9 provided by the invention, the problems that in the prior art, a combined medicine for treating tuberculosis cannot achieve a very good antibacterial effect, and a new way for treating the tuberculosis is lacked, are solved, the compound X9 is high in antibacterial activity, can achieve an excellent antibacterial effect at a relatively low concentration, and can achieve a synergistic antibacterial effect with rifampin, linezolid and bedaquiline. The compound X9 has relatively high binding power with a germ target protein, and is non-toxic to cells. The compound can be used for providing a new way for treating the tuberculosis, and can be combined with the existing tuberculosis medicines for treatment to achieve a better antibacterial effect.

The invention discloses an intermediate for preparing bedaquiline and a preparation method therefor. The intermediate disclosed by the invention has the advantages that the intermediate avoids hydrogenation and enolization of an alpha-site in the intermediate, reduces occurrence of side reactions, and increases the conversion rate of raw materials and the total yield of reaction, and is suitable for large-scale industrial production. The intermediate for preparing bedaquiline is characterized by being a compound with a structural formula (9) or an optical isomer thereof: FORMULA is shown in the description.

This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the anti-TB compound bedaquiline, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of a pathogenic mycobacterial infection.

The invention relates to a method for purifying bedaquiline and preparing a stable crystal form. After dissociating the bedaquiline-binaphthol phosphate salt obtained by the resolution with alkaline water to remove the resolution reagent, extract and concentrate with toluene to obtain an oily substance, add ketone and stir to dissolve; then add alcohol and purified water dropwise, and stir evenly , Precipitating powdery crystals of bedaquiline free base. The method of the invention refines and purifies the bedaquiline free base by using a mixed solvent, so that the impurity content is significantly reduced, the quality requirement of the finished product is met, and a stable crystal form is obtained, which is convenient for storage and a subsequent salt-forming process. The process of the invention has the advantages of simple and convenient operation, high product yield and good quality, and is suitable for industrialized production.

The invention relates to a method for separating and analyzing optical isomers of bedaquiline, belonging to the field of liquid chromatography. The method is reversed-phase high-performance liquid chromatography; a selected chromatographic column is an amphoteric ion exchange chiral column; the column temperature of the chromatographic column is 9-20 DEG C; a mobile phase is a mixed solution of 2mL to 3 mL of diethylamine, 1.5 mL to 2.5 mL of formic acid and 1000 mL of methanol; the velocity of the mobile phase is 0.08 mL / min to 0.12 mL / min; a detection wavelength is 220 nm to 230 nm; the resolution of a (1S, 2R)-bedaquiline peak and a (1R, 2S)-bedaquiline peak on a chromatogram is greater than 1.5. The method of the invention can effectively separate (1R, 2S)-bedaquiline and / or (1S, 2R)-bedaquiline, and / or detect the purity and / or the content of (1R, 2S)-bedaquiline and the purity of (1S, 2R)-bedaquiline.

The invention discloses a method for preparing (1R, 2S)-bedaquiline and (1S, 2R)-bedaquiline and belongs to the technical field of chemical synthesis. The method comprises the steps of subjecting (1R,2R)-bedaquiline and (1S, 2S)-bedaquiline to a Lewis acid action to form carbenium ions, then, subjecting the carbenium ions to action by OH<-> in an alkaline solution to form novel chiral tertiary alcohol, and then, carrying out resolution, thereby preparing (1R, 2S)-bedaquiline. According to the method, the number of reaction steps is small, the production efficiency is greatly increased, the (1R, 2S)-bedaquiline of relatively high yield is easy to obtain, and thus, the industrial production is facilitated; and meanwhile, the impurity residual is low, the purity of target products is high, and dangerous steps such as high-pressure hydrogenation are not required to be added, so that the entire production process is high in safety.

The invention discloses a preparation method for bedaquiline. The preparation method comprises the following steps: enabling a compound (9) to be reacted with a reducing agent in a solvent; and then collecting racemate of bedaquiline from a reaction product. The preparation method has the advantages that the compound (9) is a novel compound which has not been reported in literature; the racemate of bedaquiline is prepared from a compound (8) and the compound (9); the obtained product is greatly increased in yield (greater than 47%) which is remarkably greater than the yield (26%) in the original patent; and the obtained racemate of bedaquiline is high in purity, stable and controllable in quality, and beneficial for subsequent resolution reaction, and has relatively great positive effects and relatively high practical application value. The reaction formula is shown as follows: a FORMULA as shown in the description.

Practical assays to identify compounds that overcome the resistance of M. tuberculosis to bedaquiline are based on transcription factors Rv0324 and Rv0880 shown to mediate this resistance.