2021 results about "Piperidine" patented technology

The present invention relates to four specific macrocyclic compounds for use as inhibitors of KRAS mutant for the treatment of cancer. Example (1): 1-[4-(dimethylamino)-4-methyl-pent-2-ynoyl]-N-[(1S)-1-[[(6S,8S,14S)-22-ethyl-25-fluoro-(21M)-21-[2-[(1S)-1-methoxyethyl]-3-pyridyl]-18,18-dimethyl-9,15-dioxo-5,16-dioxa-2,10,22,28-tetrazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),20,23(27),24-tetraen-8-yl]carbamoyl]-2-methyl-propyl]-4-fluoro-N-methyl-piperidine-4-carboxamide.

The invention relates to a crystal form of a benzothiophene substituted fused ring compound and a preparation method thereof. Specifically, the invention provides a crystal form A and a crystal form D of 2-amino-7-fluoro-4-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxyl)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptano-2-yl) benzo [b] thiophene-3-formonitrile, and the crystal form A and the crystal form D have the advantages that the crystal form A and the crystal form D are good in stability; and the medicine can be better used for clinical treatment. # imgabs0 #

The invention relates to a pharmaceutically acceptable salt of a fused ring compound, and a crystal form and application thereof. Specifically, the present disclosure provides a pharmaceutically acceptable salt of 3-chloro-5-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxy)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptan-2-yl)-4-(trifluoromethyl) aniline, a crystal form, and a preparation method thereof, and a preparation method thereof. Corresponding salts have good stability and can be better used for clinical treatment. # imgabs0 #

The invention relates to a pharmaceutically acceptable salt of a fused ring compound, and a crystal form and application thereof. Specifically, the present disclosure provides a pharmaceutically acceptable salt of 3-chloro-5-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxy)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptan-2-yl)-4-(trifluoromethyl) aniline, a crystal form, and a preparation method thereof, and a preparation method thereof. Corresponding salts have good stability and can be better used for clinical treatment. # imgabs0 #

The invention relates to a crystal form of a benzothiophene substituted fused ring compound and a preparation method thereof. Specifically, the invention provides a crystal form E, a crystal form G and a crystal form H of 2-amino-7-fluoro-4-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxyl)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptano-2-yl) benzo [b] thiophene-3-formonitrile, and the crystal form E, the crystal form G and the crystal form H have the advantages that the stability is good; and the medicine can be better used for clinical treatment. # imgabs0 #

The invention relates to a pharmaceutically acceptable salt of a fused ring compound, and a crystal form and application thereof. Specifically, the present disclosure provides a pharmaceutically acceptable salt of 3-chloro-5-((5S, 5aS, 6S, 9R)-1-fluoro-12-((1-((4-(fluoromethylsubunit) piperidine-1-yl) methyl) cyclopropyl) methoxy)-5-methyl-5a, 6, 7, 8, 9, 10-hexahydro-5H-4-oxa-3, 10a, 11, 13, 14-pentaaza-6, 9-methylbridged naphtho [1, 8-ab] heptan-2-yl)-4-(trifluoromethyl) aniline, a crystal form, and a preparation method thereof, and a preparation method thereof. Corresponding salts have good stability and can be better used for clinical treatment. # imgabs0 #

The present disclosure relates to a pharmaceutically acceptable salt of a G12D inhibitor compound and a crystal form thereof. Specifically, provided in the present disclosure are a salt of 2-amino-4-((5S,5aS,6S,9R)-12-((1-((4-(difluoromethylene)piperidin-1-yl)methyl)cyclopropyl)methoxy)-1-fluoro-5-methyl-5a,6,7,8,9,10-hexahydro-5H-4-oxa-3,10a,11,13,14-pentaaza-6,9-methanonaphtho[1,8-ab]cyclohepten-2-yl)-7-fluorobenzo[b]thiophene-3-carbonitrile and a crystal form thereof.

Embodiments of the present invention provide methods and intermediates for the large scale preparation of 2, 4, 6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)-2-pyridyl] benzamide hemisuccinate, as well as formulations and product forms prepared by these methods. Embodiments of the present invention further provide for the preparation of lamidetan acetate (2, 4, 6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)-2-pyridyl] benzamide acetate) and / or a pharmaceutical composition thereof, and / or the use of lamidetan acetate and formulations thereof in subcutaneous drug delivery.

The invention belongs to the technical field of anion exchange membranes, and relates to a cross-linked polyaromatic piperidine anion exchange membrane and a preparation method thereof. The exchange membrane structure comprises a copolymer structure of the following repetitive structural units, the selected rigid main chain polyaromatic hydrocarbon can ensure the mechanical strength of the anion exchange membrane, meanwhile, the toughness of the anion exchange membrane is further enhanced by adopting a cross-linked structure, and a formed cross-linked network can reduce swelling of the anion exchange membrane, so that the anion exchange membrane is more stable in performance. The mechanical performance is improved; according to the invention, ether-free skeleton polyaromatic hydrocarbon is selected as a main chain and has the characteristic of strong alkali-resistant stability, six-membered nitrogen heterocyclic ions are adopted as functional groups, and a large steric hindrance structure can hinder nucleophilic substitution and elimination reaction, so that the alkali-resistant stability of the anion exchange membrane is improved, and the service life of the anion exchange membrane is prolonged. And in the # imgabs0 #, X is equal to 0.05 to 0.15.

The invention provides a low-cost flow battery and an application thereof, a redox active substance of a positive electrode electrolyte of the low-cost flow battery contains a hydroxylamine cyclic structure group with hindered amine, and the hydroxylamine cyclic structure group with hindered amine is preferably selected from 1-hydroxy-2, 2, 6, 7, 8-tetramethyl-1, 3, 5-tetramethyl-1, 3, 5-tetramethyl-1, 3, 5-tetramethyl-1, 3, 5-tetramethyl-1, 3, 5-tetramethyl-1, 3, 5-tetramethyl-1, 3, 5-tetramethyl-1, one or more of a 1-oxo-2, 2, 6, 6-tetrasubstituted piperidine group, a 1-oxo-2, 2, 6, 6-tetrasubstituted piperidine group, a 1-oxo-2, 2, 6, 6-tetrasubstituted piperidine group, and a 1-oxo-2, 2, 6, 6-tetrasubstituted piperidinium group; a redox active substance of the negative electrode electrolyte contains one or more of a titanium element, a vanadium element, a chromium element, an iron element and a zinc element. The low-cost flow battery has the advantages of high output voltage, high energy density, environment friendliness and low cost, and has good application prospects and large-scale popularization potential in the field of energy storage.

The invention provides a preparation method and application of a cobalt-based catalyst, and relates to the technical field of chemical production. The cobalt-based catalyst includes cobalt, a transition metal element, and a Group IIIA element other than aluminum. Transition metal elements and IIIA group elements except aluminum are introduced into the cobalt-based catalyst, and the electronic structure and active sites of the cobalt-based catalyst are changed. The method not only can cooperate with catalytic reaction and promote the formation and conversion of intermediates, but also can enhance the adsorption and activation capability on substrates, reduce the reaction activation energy and guide the reaction to be carried out along a specific path. Finally, the effect of efficiently harvesting the 2-methyl pentamethylene diamine and the 3-methylpiperidine at the same time is achieved.

The invention discloses a preparation method of a GLP-1R agonist Orforglipron, which comprises the following reaction steps: carrying out four-step reaction on an oxopiperidine compound (1) and (4-fluoro-3, 5-dimethylphenyl) hydrazine (2) to obtain a compound 8, and carrying out seven-step reaction on 5-bromo-indolecarboxylic acid (9) to obtain a compound 17. Then, the compound 8 and a compound 17 are subjected to an acid amine condensation reaction, and Orforglipron (LY3502970) is obtained. The preparation method is relatively low in cost, easy to operate, relatively short in synthetic route and suitable for industrial production and application, and the total yield can reach 32%.

The invention provides a polymer, a cross-linked anion exchange membrane and a preparation method and application thereof. According to the polymer and the cross-linked anion exchange membrane, aryl compounds, trifluoroketone compounds and N-methylpiperidone are polymerized to form a main chain, the main chain has excellent rigidity and flexibility, a quaternary ammonium salt alkenyl compound is introduced as a cross-linking agent, cross-linking is completed through heating in the membrane forming process, and the cross-linked anion exchange membrane is prepared. The quaternary ammonium salt side chain introduced into the side chain has excellent hydrophilic and hydrophobic phase separation characteristics. The polymer and the cross-linked anion exchange membrane have excellent oxidation-reduction resistance and alkali resistance, have the characteristics of stable physical and chemical properties, excellent ion flux, excellent mechanical properties (the elongation at break is greater than 60%) and simple process, and can be widely applied to the fields of hydrogen production by water electrolysis and the like.

The invention relates to an anion exchange membrane based on isopropyl piperidone and biphenyl and a preparation method of a membrane electrode, the preparation method comprises the following steps: respectively dissolving an aromatic monomer and IPD in a first solvent, and mixing to obtain a mixed solution, the aromatic monomer being BP or TP; dropwise adding an acidic initiator into the mixed solution for reaction at the reaction temperature of-5 DEG C to 0 DEG C to obtain a nitrogen heterocyclic ring polymer intermediate; adding a quaternization reagent into the nitrogen-containing heterocyclic ring polymer intermediate to realize quaternization modification of nitrogen atoms to obtain a quaternization ionomer; and forming a film to obtain the AEM film. The preparation method of the membrane electrode comprises the following steps: respectively forming a cathode catalyst layer and an anode catalyst layer on two opposite sides of an AEM membrane through ultrasonic spraying to obtain the MEA. The AEM membrane and the MEA obtained according to the invention have the characteristics of excellent stability and high water electrolysis performance, can significantly improve the efficiency and durability of AEMWE, and are suitable for the fields of hydrogen production by water electrolysis and the like.

Compounds of formula (II) and formula (I) which are inhibitors of QPCTL and QPCT: (II) and (I) are provided herein. Also provided are pharmaceutical compositions containing this compound, as well as compounds for use in methods of treating cancer, neurodegenerative, inflammatory or autoimmune diseases. Exemplary compounds are, for example, 3-(6-fluoropyridin-3-yl)-2-[4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]benzonitrile (Example 1): (1), and pharmacological data are provided. TIFF2025524039000368.tif70128

The invention provides a synthesis method of 6-(t-butyloxycarboryl)-3, 6-diazabicyclo [3.1. 1] heptane, which comprises the following steps: starting from N-benzyl-2, 6-piperidinedione, firstly forming a dibromide 1, then forming a bridge ring intermediate 2 under alkaline conditions, then removing benzyl to obtain an intermediate 3, then reducing dicarbonyl to form free amine 4, and finally synthesizing the 6-(t-butyloxycarboryl)-3, 6-diazabicyclo [3.1. 1] heptane. Then performing Boc protection on amino to obtain an intermediate 5, and performing debenzylation to form a target product. According to the synthesis method, few impurities are generated, and the product is easy to purify and high in purity, so that the total yield is increased, the unit cost is effectively reduced, and large-scale industrial production is facilitated.

The invention belongs to the technical field of biological catalysis, and particularly relates to four R-transaminase and application thereof in asymmetric synthesis of chiral N-heterocyclic amine active drug intermediates. The amino acid sequences of the R-transaminase disclosed by the invention are shown as SEQ ID NO. 1, SEQ ID NO. 3, SEQ ID NO. 5 and SEQ ID NO. 7. Four kinds of R-transaminase are obtained through gene mining and screening, and recombinant escherichia coli is constructed and expressed by adopting a gene engineering technology. The obtained R-transaminase can be used for synthesizing chiral drug intermediates (R)-3-amino-N-Boc-pyrrole (1b) and (R)-3-amino-N-Boc-piperidine (2b) with high stereoselectivity, and has a good application prospect.

Provided is an anthraquinone derivative represented by formula (9-1). In formula (9-1), R1 and R2 are each independently an amino group or a hydroxyl group and Y1, Y2, and Z are each independently a hydrogen atom, a C1-C10 alkyl group, a C1-C10 alkoxy group, a cyano group, a nitro group, a halogen atom, a C1-C10 halogenated alkyl group, an amino group, an alkylamino group, a piperidyl group, an aryl group, or a cyclohexyl group, the aryl and cyclohexyl groups being optionally substituted.　

The invention discloses an antibacterial peptide simulant based on adamantane modification and application of the antibacterial peptide simulant. The preparation method comprises the following steps: performing amide condensation on Fmoc amino acid to obtain a compound of which the carboxyl terminal is modified by amantadine or Boc protected aliphatic amine, and then removing an Fmoc group by piperidine to obtain a series of amantadine modified crude products and Boc protected aliphatic amine modified intermediate compounds; the intermediate compound is subjected to amide condensation to obtain a compound of which the amino terminal is further modified by adamantanic acid, then other protecting groups are cracked by trifluoroacetic acid to obtain a series of adamantanic acid modified crude products, and the crude products are purified to obtain the adamantane modified peptidomimetic. The adamantane modified peptidomimetic is used for preparing drugs for treating infectious diseases caused by sensitive bacteria and drug-resistant bacteria, has efficient antibacterial activity and low toxicity, and is not influenced by a traditional drug-resistant mechanism.

The present invention provides a compound of Formula (I):or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds; and methods of using such compounds for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2).

The present application provides an electrolytic solution for magnesium batteries, a method for preparing the same, and a magnesium battery, comprising a non-aqueous solvent and an electrolyte salt, wherein the non-aqueous solvent is selected from one or more of imidazole ionic liquids, pyrrole ionic liquids, piperidine ionic liquids, ether compounds, ester compounds, pyridine compounds, nitrile compounds, sulfone compounds, or ketone compounds; the electrolyte salt has a chemical formula [MgmLinXo(HMDS)2m+m−oRp]·Mq. The electrolytic solution for magnesium batteries provided by the present application is endowed with good stability, strong water resistance and impurity resistance, and excellent electrochemical performance under the mutual synergistic effect among the components, and excellent electrochemical performance under the mutual synergistic effect among the components, and at the same time, the electrolytic solution can promote reversible deposition-dissolution of magnesium, reduce the over-potential, inhibit formation of a passivation layer of magnesium salts on the surface of the anode, and increase the charging-discharging specific capacity and cycling stability of the magnesium battery.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

The invention relates to a high-efficiency preparation method of a Ritlecitinib key intermediate, which comprises the following steps: reacting (2S)-1-substituent-2-methylpiperidine-5-ketone with 4-amino-7H-pyrrolo [2, 3, d] pyrimidine to form imine, and carrying out chiral induction on the imine in the presence of a reducing agent to obtain a single chiral 4-(N-((3R, 3R)-4-(4-((3R, 3R)-4-(4-amino-7H-pyrrolo [2, 3, d] pyrimidine-5-ketone)-4-amino-7H-pyrrolo [2, 3, d] pyrimidine-5-ketone)-4-amino-7H-pyrrolo [2, the preparation method comprises the following steps: adding 2-(2, 6, 6, 6, 6-tetramethylpiperidine-3-yl)) amino-7H-pyrrolo [2, 3, d] pyrimidine into a reaction kettle, and carrying out deprotection to obtain a target product. Compared with the existing method, the method has the characteristics of short synthetic route, good selectivity, easiness in industrialization and the like.

The invention relates to the technical field of fluorescent probes, and provides a low-concentration ratio type high-concentration enhanced fluorescent probe as well as a preparation method and application thereof in order to solve the problems that a traditional fluorescent probe depends on a high-concentration use condition and is often faced with fast probe consumption, increased biotoxicity, non-specific target binding and the like in a biological sample. The preparation method of the fluorescent probe comprises the following steps: step 1, preparing phenothiazine dialdehyde; and 2, mixing phenothiazine dialdehyde, malononitrile, ethanol, acetonitrile, DMF and piperidine, and carrying out a reflux reaction to obtain the low-concentration ratio-type high-concentration enhanced fluorescent probe. The probe provided by the invention realizes quantitative detection of HClO through synchronous change of two emission channels, and the detection sensitivity and reliability are remarkably improved; when the concentration is high, an enhanced single-channel fluorescence amplification effect is shown, and strong signal identification and macroscopic visual imaging in specific application are facilitated, so that the dual requirements of trace monitoring and high-throughput screening are met.

The invention provides a 4 (1H-pyrazol-3-yl) piperidinyl derivative, the structural formula of the 4 (1H-pyrazol-3-yl) piperidinyl derivative is shown as a formula I, # imgabs0 #, R1 is an aromatic ring or a substituted aromatic ring, the substituted aromatic ring is a substituent group on the aromatic ring, and R2 is a hydrogen atom or a hydrogen atom or a substituent group on the substituted aromatic ring, so that the structural formula of the 4 (1H-pyrazol-3-yl) piperidinyl derivative is shown as a formula I; the substituent groups are selected from C1-C6 alkyl groups, C1-C6 halogenated alkyl groups, C1-C6 alkylamino groups, C1-C6 alkoxy groups, five-membered to six-membered heterocyclic groups, halogen, hydroxyl groups, cyano groups, nitryl groups, amino groups and carbonyl substituted five-membered to six-membered heterocyclic groups containing 1-2 nitrogen atoms; and R2 is H or a C1-C6 alkyl group. The 4 (1H-pyrazol-3-yl) piperidinyl derivative has MNK1 and / or MNK2 inhibitory activity, and has anti-cancer and anti-inflammatory activity; the invention also provides a preparation method of the 4 (1H-pyrazol-3-yl) piperidinyl derivative, an application of the 4 (1H-pyrazol-3-yl) piperidinyl derivative in preparation of MNK1 and / or MNK2 inhibitors, and an application of the 4 (1H-pyrazol-3-yl) piperidinyl derivative in preparation of anti-inflammatory and anti-cancer drugs.

The invention belongs to the technical field of bioengineering, and relates to a transaminase mutant, a recombinant genetically engineered bacterium and application of the transaminase mutant in catalytic synthesis of (R)-1-Boc-3-aminopiperidine.The transaminase mutant is obtained by conducting single-point or combined mutation on the 131 site and / or the 197 site of an amino acid sequence shown in SEQ ID NO.2; the mutation sites comprise that the 131 phenylalanine is mutated into aspartic acid, threonine or tyrosine, and / or the 197 lysine is mutated into arginine or leucine. Experimental results show that compared with wild type transaminase, the catalytic activity, the thermal stability and the organic solvent tolerance of the obtained mutants, especially single-point mutants MyTA1-F131Y and MyTA1-K197R and a combined mutant MyTA1-F131Y-K197R, are all remarkably improved, and compared with the wild type transaminase, the catalytic activity, the thermal stability and the organic solvent tolerance of the obtained mutants are all remarkably improved. The mutant MyTA1-F131Y-K197R can be used for efficiently catalyzing asymmetric amination of N-Boc-3-piperidone to synthesize (R)-1-Boc-3-aminopiperidine, the conversion rate of the (R)-1-Boc-3-aminopiperidine after the (R)-1-Boc-3-aminopiperidine reacts for 24 hours under the condition that the substrate concentration is 100 g / L can reach 90% or above, and the mutant MyTA1-F131Y-K197R has a good industrial application prospect.

The invention discloses an omega-transaminase progenitor enzyme mutant for efficient catalytic synthesis of (R)-chiral amine compounds and application, and relates to the technical field of molecular biology. The omega-transaminase mutant is obtained by mutating an ancestor enzyme Ancaa-101 of omega-transaminase from Aspergillus terreus, and the amino acid sequence of the omega-transaminase mutant is as shown in SEQ ID NO. 6. The invention also discloses a preparation method of the omega-transaminase mutant. Compared with an ancestor enzyme, the activity of the omega-transaminase ancestor enzyme mutant on a non-natural substrate, namely 1-acetyl naphthalene, N-tert-butyloxycarboryl-3-piperidone or 3-oxopyrrolidine-1-carboxylic acid tert-butyl ester, is remarkably improved.

Methods for treating itch in human patients with atopic dermatitis (AD) and / or prurigo nodularis (PN) comprising administering a therapeutically effective amount of at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3- yl)piperazin-1-yl]pent-2-enenitrile (rilzabrutinib) and pharmaceutically acceptable salts thereof are disclosed.