25 results about "Phenylpiperidine" patented technology

The invention discloses an aldehyde reductase mutant and application thereof in synthesis of a dexmethylphenidate hydrochloride intermediate, and belongs to the field of molecular biology and enzyme engineering. The aldehyde reductase mutant, polynucleotide for coding the mutant, and the recombinant expression vector can express the aldehyde reductase mutant and are used for constructing a recombinant cell or a recombinant strain for expressing the aldehyde reductase mutant. The provided aldehyde reductase mutant can catalyze 2-phenyl-2-((R)-piperidine-2)-acetaldehyde into (R)-2-phenyl-2-((R)-piperidine-2)-1-ethanol, especially improves the stereoselectivity of (R)-2-phenyl-2-((R)-piperidine-2)-1-ethanol, solves the problems of strict conditions, complex reaction and high cost in the existing synthesis method, and has a wide application prospect in the field of synthesis of (R)-2-phenyl-2-((R)-piperidine-2)-1-ethanol. Wide application prospects are realized.

Provided herein are solid forms and methods of prepapation relating to (R) -3- (tert-butyl) -N-(1- (4- (6- (6- (4- ( (1- (4- (2, 4-dioxotetrahydropyrimidin-1 (2H) -yl) phenyl) piperidin-4-yl) methyl) piperazin-1-yl) pyridin-3-yl) -7H-pyrrolo [2, 3-d] pyrimidin-4-yl) -2-methylphenyl) ethyl) -1,2,4-oxadiazole-5-carboxamide.

This disclosure provides compounds of formula (I) or pharmaceutically acceptable salts thereof, methods for preparing the same, and their use in the treatment and / or diagnosis of cancers such as neuroblastoma, prostate cancer, pancreatic cancer, leukemia, osteosarcoma, hepatoblastoma, lung cancer, colon cancer, breast cancer, skin cancer, thyroid cancer, and / or rhabdoid cancer. JPEG2026522940000099.jpg50170

The present invention provides a compound having the structure:whereinR1, R2, R3, R4, and R5 are each independently H, halogen, CF3 orC1-C4 alkyl;R6 is H, OH, or halogen;B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole,wherein the heterobicycle is other than chloro substituted indole; andthe pyrazole, when substituted, is substituted with other than trifluoromethyl,or a pharmaceutically acceptable salt thereof.

The present invention relates to a pharmaceutically acceptable salt and a crystal form of a tetrahydronaphthalene derivative, and a preparation method. Specifically, the present disclosure provides a pharmaceutically acceptable salt and a crystal form of (S)-3-(5-(4-((1-(4-((1R,2R)-6-hydroxy-2-isobutyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenyl)piperidin-4-yl)methyl)piperazin-1-yl)-1-oxoisoindolin-2-yl)piperidine- 2,6-dione, and a preparation method therefor. The corresponding salt has good stability and can be better used for clinical treatment.

The present invention provides a compound having the structure:whereinR1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl;R6 is H, OH, or halogen;B is a substituted or unsubstituted heterobicycle,pyridazine, pyrazole, pyrazine, thiadiazole, or triazole,wherein the heterobicycle is other than chloro substituted indole; andthe pyrazole, when substituted, is substituted with other than trifluoromethyl,or a pharmaceutically acceptable salt theref.

The invention relates to a CDK drug intermediate 3-(3-bromophenyl) piperidine-2, 6-diketone as well as a synthesis method and application thereof, and belongs to the technical field of medicine synthesis. The synthetic method of the CDK drug intermediate 3-(3-bromophenyl) piperidine-2, 6-diketone provided by the invention comprises the following steps: (1) mixing 3-bromobenzyl cyanide and acrylonitrile, slowly dropwise adding benzyltrimethylammonium hydroxide, and refluxing to obtain an intermediate 2-(3-bromophenyl) glutaronitrile; and (2) dissolving the intermediate 2-(3-bromophenyl) glutaronitrile in an acetic acid-concentrated sulfuric acid solution, and carrying out hydrolysis cyclization to obtain the target compound 3-(3-bromophenyl) piperidine-2, 6-diketone. According to the invention, 3-bromophenylacetonitrile is used as an initial raw material, and a target product is prepared only through two simple steps. The method has the advantages of easily available raw materials, short reaction route, simple post-treatment and the like, and is suitable for industrial preparation and production.

The application relates to a compound containing a nitrogen-containing azetidinyl phenyl piperidine-2,6-dione structure, a pharmaceutical composition and application thereof. The compound containing the nitrogen-containing azetidinyl phenyl piperidine-2,6-dione structure has a structure shown in formula (I). The compound has improved proliferation inhibition activity on cancer cells and degradation effect on proteins such as GSPT1, and has practical value.

This invention discloses a method for synthesizing a key intermediate compound of rumepiride and its preparation, belonging to the field of pharmaceutical intermediates technology. This invention discloses for the first time a novel rumepiride-specific key intermediate, 1-(4-fluorophenyl)-4-(4-piperidinone-1-yl)but-1-one, whose structure is precisely adapted to the requirements of constructing the tetracyclic core of rumepiride, exhibiting excellent chemical stability and reactivity. This invention provides two independent preparation processes for γ-hydroxybutyric acid and γ-aminobutyric acid, adaptable to different raw material supply scenarios. The high-purity intermediate is prepared through halogenation, Friedel-Crafts acylation, nucleophilic condensation or double addition, Dickmann condensation, and hydrolysis decarboxylation steps. The process of this invention is simple to operate, has mild conditions, few side reactions, and stable yield. The purity of the prepared intermediate is ≥99.5%, and the impurity index meets the application standards for high-end active pharmaceutical ingredients. It can directly undergo a cyclization reaction with 2-(methylamino)phenylhydrazine to construct the rumepiride nucleus, effectively solving the pain points of existing technologies such as cumbersome processes, low yield, and difficulty in controlling impurities. It fills a technological gap in the industry and has extremely high industrial production value and patent application prospects.

The application provides a preparation method of ethperidol hydrochloride. First, p-ethylbenzoic acid is condensed with piperidine under the action of a chlorinating reagent to obtain (4-ethylphenyl)(piperidin-1-yl)methanone, and then ethperidol is synthesized by one-pot reaction of (4-ethylphenyl)(piperidin-1-yl)methanone and isopropenylmagnesium bromide. The reaction steps are few, and ethperidol hydrochloride can be obtained without column chromatography, the purity of ethperidol hydrochloride reaches 99.9%, and the content of isomer impurities in ethperidol raw medicine is reduced.

In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The invention relates to the technical field of difenidol hydrochloride production, in particular to a preparation method of difenidol hydrochloride. The preparation method comprises the following steps: S1, preparing a 1-(3-chloropropyl) hexahydropiperidine crude product; s2, a, a-diphenyl-1-piperidine butanol is prepared; and S3, preparing difenidol hydrochloride. According to the preparation method of difenidol hydrochloride provided by the invention, related impurities such as alkene compounds can be reduced, and meanwhile, a relatively good yield is ensured.

This invention provides a method for preparing high-purity piminodin, relating to the field of piminodin preparation. The method includes: a first nucleophilic substitution of 1,3-dibromopropane and aniline, followed by deprotection treatment of 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride, hydrolysis, esterification, and a second nucleophilic substitution to obtain crude piminodin, which is then purified to obtain piminodin with a purity greater than 99.9%. This invention uses readily available commercial raw materials and shortens the synthetic route compared to existing methods, significantly improving synthetic efficiency. In the intermediate synthesis process, each reaction step has only one reaction site. In the deprotection process, palladium on carbon is used as a catalyst to improve the reaction yield. Simple treatment allows for direct vacuum concentration, overcoming the low yield problem of existing deprotection steps. The purification process removes most impurities through natural volatilization of n-hexane, and after two recrystallizations, the purity of the piminodin product is greater than 99.6%, with a single impurity content of less than 0.2%.

The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl) phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.

The present disclosure provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, a preparation method thereof, and use thereof in the treatment and / or diagnosis of cancers such as neuroblastoma, prostate cancer, pancreatic cancer, leukemia, osteosarcoma, hepatoblastoma, lung cancer, colon cancer, breast cancer, skin cancer, thyroid cancer and / or rhabdomyoid cancer.

Provided are salts of 2-phenyl-2- (piperidin-2-yl) acetamide, particularly of essentially enantiomerically pure (S, S) -and (R, R) -2-phenyl-2- (piperidin-2-yl) acetamide (L-threo-PPAA and D-threo-PPAA respectively), with a resolving agent, optionally as solvates, efficient methods for manufacturing them starting from a mixtures comprising the (R,R)-and (S,S)-enantiomers, and uses thereof.

Provided herein are methods of preparing Compound A having the name of (R) -3- (tert-butyl) -N- (1- (4- (6- (6- (4- ( (1- (4- (2, 4-dioxotetrahydropyrimidin-1 (2H) -yl) phenyl) piperidin-4-yl) methyl) piperazin-1-yl) pyridin-3-yl) -7H-pyrrolo [2, 3-d] pyrimidin-4-yl) -2-methylphenyl) ethyl) -1,2, 4-oxadiazole-5-carboxamide or the following chemical structure (I) and pharmaceutically acceptable salts thereof.

The present invention provides a compound having the structure:whereinR1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl,wherein two or more of R1, R2, R3, R4, or R5 are other than H;R6 is H, OH, or halogen; andB is a substituted or unsubstituted heterobicycle,wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is Cl, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is Cl, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other thanor a pharmaceutically acceptable salt thereof.

The invention discloses a preparation method of a niraparib intermediate (S)-3-(4-aminophenyl) piperidine-1-tert-butyl formate, and belongs to the technical field of medicine synthesis. According to the method, 4-(3-pyridyl) aniline is taken as an initial raw material, and a target product is prepared through amino protection, pyridinium salt synthesis, hydroboration reduction, ruthenium catalysis asymmetric hydrogenation, deprotection / salification and t-butyloxycarbonylation reaction in sequence. The chiral center is directly constructed by innovatively adopting the ruthenium-catalyzed asymmetric hydrogenation reaction, so that the method has excellent stereoselectivity, and the obvious defects of the traditional resolution process are overcome; by optimizing reaction conditions and post-treatment processes, high-yield and high-purity product preparation is realized; the whole technological process is easily available in raw materials, simple to operate and suitable for industrial production; meanwhile, the method has the characteristics of environmental protection, economy and high efficiency.

The present invention provides a compound having the structure:whereinR1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl,wherein two or more of R1, R2, R3, R4, or R5 are other than H;R6 is H, OH, or halogen; andB is a substituted or unsubstituted heterobicycle,wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is Cl, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is Cl, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other thanor a pharmaceutically acceptable salt thereof.

A pharmaceutical composition containing 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid (Compound A) or a pharmaceutically acceptable salt or co-crystal thereof as an active ingredient, wherein a content of Compound A is 30% by weight or more based on a total weight of the pharmaceutical composition. The pharmaceutical composition is preferably obtained using a production method that includes a granulation step of obtaining a granulated product by spraying a binding solution containing Compound A or a pharmaceutically acceptable salt or co-crystal thereof and a binder onto a powder containing Compound A or a pharmaceutically acceptable salt or co-crystal thereof in a fluidized bed granulator

The application discloses a fluorophenyl piperidone compound and a derivative and a pharmaceutical application thereof, which can specifically activate a TGR5 receptor, pass through a blood-brain barrier, and be used for preventing or treating central nervous diseases such as chronic pain, anxiety, depression and the like in which the TGR5 receptor is involved.

The present invention relates to pharmaceutically acceptable salts, crystalline forms, and preparation methods of tetralin derivatives. Specifically, the present disclosure provides pharmaceutically acceptable salts, crystalline forms, and preparation methods for (S)-3-(5-(4-((1-(4-((1R,2R)-6-hydroxy-2-isobutyl-1,2,3,4-tetralin-1-yl)phenyl)piperidin-4-yl)methyl)piperazin-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, which have good stability and can be used in clinical treatment.

A phenylpiperidine compound and a use thereof. The phenylpiperidine compound is a compound represented by formula (0), or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a prodrug, or a pharmaceutically acceptable salt or ester thereof. Also provided is a use of the phenylpiperidine compound in preparation of drugs for treating ophthalmic diseases.