269 results about "Quinolizine" patented technology

The present application provides a therapeutic combination of a quinoline derivative and an antibody, which comprises an immune checkpoint inhibitor and a tyrosine kinase inhibitor, wherein the tyrosine kinase inhibitor is a compound of formula I or a pharmaceutically acceptable salt thereof. The therapeutic combination in the present application shows good activity against lung tumor and liver tumor.

The present disclosure relates to a crystalline form of trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic acid hydrochloride, methods of preparation, and its use as a therapeutic agent to treat inflammatory diseases.

The present disclosure relates to a crystalline form of trans-4-[1-(3-Chloro-phenyl)-7-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimido[5,4-c]quinolin-3-yl]-cyclohexanecarboxylic acid hydrochloride, methods of preparation, and its use as a therapeutic agent to treat inflammatory diseases.

The application discloses an 8-hydroxyquinoline anticancer zinc (II) complex and a synthesis method and application thereof. The 8-hydroxyquinoline anticancer zinc (II) complex is synthesized by taking 5,7-diiodo-8-hydroxyquinoline, 5,7-dichloro-8-hydroxyquinoline, 5-chloro-7-iodo-8-hydroxyquinoline, 5,7-dibromo-8-hydroxyquinoline and 5-chloro-8-hydroxyquinoline as a first ligand and taking 4,4'-dimethoxy-2,2'-bipyridine, 4,4-di-tert-butyl-2,2-bipyridine, 5,5'-dimethyl-2,2-bipyridine, 2,2-bipyridine and 4,4'-dimethyl-2,2'-bipyridine as auxiliary ligands. The 8-hydroxyquinoline anticancer zinc (II) complex has good inhibiting effect on SK-OV-3CR cells of an ovarian cancer drug-resistant strain, is higher than that of cisplatin drugs, overcomes drug resistance of clinical drugs, has potential medicinal value and can be used for preparation of various antitumor drugs.

Disclosed herein is an isoquinoline-1 (2H)-one derivative of formula (I): or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof wherein the values of the variables (e.g., L2A, R1, R2A, R3, R4A, R4B, R4C, R4D, Q2, Q3, Q4) are as described herein. Also disclosed is a pharmaceutical composition comprising such derivatives, and a method of using such derivatives to treat or prevent a condition or disease responsive to inhibition of PI3K [alpha] activity in a subject.

The present invention relates to a process for preparing the compound of Formula I in the form of a base or a salt thereof, and its use as an intermediate for the preparation of calcitonin gene- related peptide (CGRP) receptor antagonist active pharmaceutical ingredients, in particular zavegepant, where the compound of Formula I is the following: (I)

The present invention relates to compound according to formula (I), (I) which is a positive allosteric modulator of D1 and accordingly of benefit as pharmaceutical agent for the treatment of diseases in which D1 receptors play a role.

The present application relates to the technical field of lithium ion battery, in particular to a kind of lithium ion battery electrolyte additive and its electrolyte and lithium ion battery, the additive structural formula is as follows: Wherein, Ar is selected from any one of phenyl, pyridyl or quinoline group;R1, R2 Same or different, R1 And R2 respectively independently selected from any one of hydrogen, fluorine, cyano, C1~C5 Alkyl, C1~C4 Alkoxy, fluorine-containing C1~C4 Alkoxy, x is selected from 1, 2 or 3;Y, z respectively selected from 1, 2, 3 or 4, x+y+z≤6, and Ar is phenyl, x=1, R1 And R2 are not hydrogen simultaneously.The additive can form stable SEI film on the negative electrode surface, reduce the impedance of battery, improve the low temperature performance of battery, and also have flame-retardant function.

The invention provides novel 5-membered heteroaryl derivatives of quinolinones that inhibit Werner Syndrome ATP dependent helicase enzyme (WRN) activity. The invention also provides pharmaceutical compositions comprising compounds of the invention and methods thereof for treating various diseases and disorders associated with or related to WRN activity, such as various types of cancer.

The present invention addresses the problem of providing a medicine that, despite of being a non-ergot dopamine agonist (DA), reduces the risk of the drowsiness side effect, and exhibits an excellent therapeutic effect on neurodegenerative disorders such as Parkinson's disease (PD). The present invention relates to a pharmaceutical composition for treating neurodegenerative diseases such as Parkinson's disease, the pharmaceutical composition comprising 1-{[(4aR,6R,8aR)-2-amino-3-cyano-8-methyl-4,4a,5,6,7,8,8a,9-octahydrothieno[3,2-g]quinolin-6-yl]carbonyl}-3-[2-(dimethylamino)ethyl]-1-propylurea or a pharmacologically acceptable salt thereof. The pharmaceutical composition is characterized by being orally administered at a daily dose of 0.25 mg to 2 mg in terms of free form.

The invention belongs to the technical field of pharmacy, and particularly relates to application of polycyclic alkaloid in preparation of an anti-breast cancer drug, and the polycyclic alkaloid is 1, 2a, 7-trimethyl-5-tosyl-1, 2, 2a, 3, 4, 5-hexahydropyrrolo [4, 3, 2-de] quinoline. The polycyclic alkaloid compound is applied to preparation of anti-breast cancer drugs, the effect of inhibiting growth of breast cancer cells is remarkable, and the efficacy of the polycyclic alkaloid compound is far better than that of a positive drug ML162 aiming at EC50 (mu M) + / -S.D = 9.04 + / -0.37 of HCC1937 human breast cancer cells.

The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a small ubiquitin-like modifier (SUMO) activating enzyme (SAE) inhibitor, such as [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxy-cyclopentyl]methyl sulfamate (Compound I-263a) or a pharmaceutically acceptable salt, in combination with one or more anti-CD19 antibodies. Also provided are medicaments for use in treating cancer.

The invention belongs to the field of metal ion battery material synthesis, and particularly provides a sulfur-doped oxygen-nitrogen-enriched conjugated organic material and application thereof in Li < + > / Zn < 2 + > ion batteries. The preparation method comprises the following steps: firstly, preparing 2, 3, 8, 9, 14, 15-hexachlorodiquinoline [2, 3-a: 2 ', 3'-c] phenazine (HANT-Cl) by taking cyclohexanehexone and dichlorobenzene diamine as raw materials, and then synthesizing 6S6O and the derivative thereof by taking HATN-Cl, sodium sulfide nonahydrate and a naphthoquinone derivative as raw materials. The obtained electrode material contains a plurality of oxidation-reduction active sites, multi-electron storage can be carried out, the transfer rate of electrons is improved through the large pi conjugated structure of the conjugated quinoneazine material, and therefore the high theoretical specific capacity and the excellent rate performance are achieved. Due to the addition of the sulfur element, the oxidation-reduction potential of the material is improved, the energy density of a battery can be improved, and the material has a wide application prospect in a Li < + > / Zn < 2 + > ion battery system.

The present invention relates to novel 2-(3-pyridin-2-yl-4-quinolin-4-yl-pyrazol-1-yl)-acetamide derivatives as potent inhibitors of transforming growth factor-beta receptor I (also known as activin receptor-like kinase 5) (TGFβRI) / ALK5. Other objects of the present invention are to provide processes for preparing these compounds; pharmaceutical compositions comprising an effective amount of these compounds; the use of said compounds for the preparation of a medicament for the treatment of pathological conditions or diseases which can be ameliorated by the inhibition of transforming growth factor-beta receptor I (TGFβRI) / ALK5, such as respiratory diseases, including idiopathic pulmonary fibrosis, asthma, COPD and lung cancer and skin and ocular fibrotic disorders.

The invention provides an application of a quinoline derivative as shown in a formula (1) in preparation of drugs for treating acute lung injury and resisting inflammation. It is found for the first time that the quinoline derivative has the function of a P2Y6R antagonist, has an obvious antagonistic effect on P2Y6R-related inflammation and can be used for preparing P2Y6R-related anti-inflammatory drugs.

This invention discloses an axially chiral 1,4'-biquinolinone and its derivatives, and a synthetic method thereof. The method uses MBH carbonate and quinoline-2(1 H Using β-ketones as raw materials, (DHQD)₂PYR as catalyst, and DME as solvent, a centrally chiral β-substituted allyl intermediate was synthesized; then, using iron powder as a reducing agent and acetic acid as solvent, enantiomeric enriched centrally chiral γ-lactam compounds were obtained; finally, using DBN as a base and DME as solvent, enantiomeric enriched compounds were obtained. (S) -Axial chiral 1,4'-biquinolinone or its derivatives. The method of this invention has mild reaction conditions, readily available raw materials, high enantioselectivity of the product, and excellent yield. The synthesized 1,4'-biquinolinone or its derivatives can be further used to synthesize novel substituted quinolinone phosphonate compounds, and to synthesize drugs with antibacterial, antimalarial, anticancer, antitumor, or herbicidal activities, showing broad application prospects.

This invention discloses a class of 2-(2-(quinolin-4-yloxy)ethyl)pyridazine-3(2H)-one compounds, their preparation methods, and applications. The structure of these compounds is shown in general formula (I). This invention also discloses that the above compounds have a significant inhibitory effect on interleukin-1 receptor-associated kinase 1 (IRAK1). These compounds can inhibit the proliferation of various tumor cells, including liver cancer, lung cancer, pancreatic cancer, gastric cancer, kidney cancer, colon cancer, esophageal cancer, glioblastoma, leukemia, multiple myeloma, and other solid tumors and hematological malignancies. This invention provides a new option for tumor treatment.

The application relates to a reagent combination for detecting depression, a manufacturing method, a detection system and application thereof, and belongs to the technical field of instrument detection. The reagent combination for detecting depression comprises a calibrator, a quality control sample and an extraction solution of a to-be-detected compound serving as a biomarker; wherein the to-be-detected compound is at least three kinds selected from 5-hydroxyanthranilic acid, methionine, gamma-aminobutyric acid, 3,4-dihydroxyphenylacetic acid, 2-picolinic acid, quinolinic acid, kynurenine, 5-hydroxytryptamine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, dopamine and norepinephrine. The reagent combination for detecting depression and the detection system can significantly improve the accuracy of diagnosis, are convenient to detect, have good repeatability of detection data, are high in specificity, and are accurate in clinical diagnosis results.

The application discloses a high-activity 8-hydroxyquinoline rhodium complex in vivo and in vitro and a synthesis method and application thereof. The 5,7-dichloro-8-hydroxy-2-methylquinoline, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, methanol, dimethyl sulfoxide and triethylamine are taken, and under a closed condition, the reaction is carried out at 80 DEG C for 3 days; after being cooled to 37 DEG C, filtration and drying are carried out, and the 5-chloro-8-hydroxyquinoline rhodium complex is obtained. The 5-chloro-8-hydroxyquinoline rhodium complex has obvious inhibiting effect on SK-OV-3 and SK-OV-3 / DDP cancer cells, shows superior antitumor activity, and has small toxicity to normal HL-7702 cells; the 5-chloro-8-hydroxyquinoline rhodium complex has potential medicinal value and is expected to be used for preparation of various antitumor drugs.

The application provides novel N-heterocyclic compounds, such as quinoline or isoquinoline compounds, preferably quinazoline compounds, as calcineurin inhibitors (CNIs,) that provide improved safety profiles, and the pharmaceutical composition and formulation thereof, as well as a method of using the N-heterocyclic compounds for the treatment of, inter alia, an inflammatory-related disease or disorder.

The present invention relates to fungicidal compositions comprising at least one compound selected from the group consisting (I-1) N-[1,3-dimethyl-1-(phenylmethyl)butyl]-8-fluoro-3- quinolinecarboxamide, (I-2) N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3- carboxamide, (I-3) N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, as active component 2) at least one compound, or an N-oxide, or an agriculturally useful salt thereof, selected from the group consisting of (II-1) 2-fluoro-4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]benzanilide, (II-2) metarylpicoxamid,(II-3) N-methoxy-N-[[4-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide, (II-4) N,2-dimethoxy-N-[[4-[5- (trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propenamide,(II-5) methyl (Z)-3-methoxy-2- (2-methyl-5-phenyl-phenoxy)prop-2-enoate, wherein the weight ratio of compound I to compound II is from 10:1 to 1:10. The invention also relates to an agrochemical composition comprising the composition and a solvent of solid carrier. Further, the invention relates to a non- therapeutic use of the inventive compositions controlling phytopathogenic harmful fungi.

The invention discloses an efficient synthesis method of brexpiprazole, which comprises the following steps: taking 4-bromo-benzothiophene and N-Boc-piperazine as initial raw materials, under the protection of nitrogen, carrying out reaction by using a supported catalyst to prepare 4-Boc piperazine benzothiophene, and then carrying out acidolysis to obtain 4-piperazine benzothiophene hydrochloride; the method comprises the following steps: reacting 3, 4-dihydro-7-hydroxy-2 (1H) quinolinone with 1-bromo-4-chloro-butane to generate 3, 4-dihydro-7-(4-chlorobutoxy)-2 (1H)-quinolinone, and then converting the 3, 4-dihydro-7-(4-chlorobutoxy)-2 (1H)-quinolinone into 7-(4-chlorobutoxy)-2 (1H)-quinolinone; then condensing with 4-piperazine benzothiophene hydrochloride to obtain a crude product of brexpiprazole; and finally, crystallizing and purifying for multiple times to obtain high-purity brexpiprazole. According to the preparation method disclosed by the invention, 4-bromo-benzothiophene and N-Boc-piperazine are taken as starting raw materials, and high-purity brexpiprazole is prepared by optimizing selection of a catalyst and conditions of each step and through an excellent purification process.

The application discloses a phosphorescent on-off type biological orthogonal iridium complex probe and a preparation and application thereof, and belongs to the technical field of organic photoelectric materials. A benz[h]quinoline-5,6-dione derivative is used as a C^N ligand, the C^N ligand is subjected to a coordination reaction with an iridium trichloride trihydrate to obtain a cyclometalated iridium chloro-bridged dimer, and then the cyclometalated iridium chloro-bridged dimer is subjected to a reaction with an N^N ligand to obtain the iridium complex probe. After the probe is reacted with a biological orthogonal unit, angelica lactone, the excited state energy level of the complex is changed, the photophysical property of the complex is influenced, the phosphorescence is turned on from nothing, and the effect of phosphorescence on-off is achieved. The phosphorescence on-off characteristic makes the probe before and after the reaction with the angelica lactone present obvious luminescent signal ratios. The characteristic can maximally reduce background signal interference, is convenient for cell imaging and biomolecular recognition, and can provide a new train of thought for developing a novel phosphorescent on-off type biological orthogonal material. The application has a good application prospect in the field of biological marking and imaging.

This invention discloses a class of quinalidine disperse yellow dyes with high sublimation fastness and their synthesis method, belonging to the field of disperse dye technology. This invention uses Disperse Yellow 54 as the parent core and introduces one of the following substituents at the 6-position of the quinalidine ring: ethyl, n-propyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, cyclopropoxy, cyclobutoxy, cyclopropylmethoxy, 2-methoxyethoxy, fluorine, chlorine, bromine, cyano, or nitro. This invention uses 6-substituted-2-methyl-3-hydroxyquinoline-4-carboxylic acid and phthalic anhydride as raw materials, and synthesizes the target dye in one step via a high-temperature condensation reaction. Experimental results show that the sublimation fastness of the dye of this invention reaches grade 4-5 or 5, significantly improved compared to Disperse Yellow 54 (grade 2-3), while maintaining excellent resistance to rubbing, perspiration, and sunlight. This invention has a simple synthesis process, high yield, and high purity, possessing extremely high industrial production value and market application prospects.

Disclosed in the present invention are a polysubstituted aminoquinoline compound and the use thereof. Specifically disclosed in the present invention is a compound as represented by formula (I), or a stereoisomer, tautomer, crystal form, pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof. The compound of the present invention is a CD38 inhibitor, and can be used in the preparation of a drug for treating and / or preventing diseases related to abnormal expression or activity of CD38.

The isoquinolin-1(2H)-one derivative of formula (I), or its stereoisomer, tautomer, or pharmaceutically acceptable salt is disclosed herein, and the variables (e.g., L 2A , R 1 , R 2A , R 3 , R 4A , R 4B , R 4C , R 4D , Q 2 , Q 3 , Q 4 ) have the values as described herein. Also disclosed are pharmaceutical compositions containing such derivatives, and methods for treating or preventing disorders or diseases responsive to inhibition of PI3Kα activity in a subject using such derivatives. TIFF2026516333000335.tif53165

The invention provides novel 5-membered heteroaryl derivatives of quinolinones that inhibit Werner Syndrome ATP dependent helicase enzyme (WRN) activity. The invention also provides pharmaceutical compositions comprising compounds of the invention and methods thereof for treating various diseases and disorders associated with or related to WRN activity, such as various types of cancer.

The present invention provides derivatives of quinolylnitrones of formula I, wherein the meaning of the substituents is as described in the description, useful in treatment and / or prevention of hearing loss.Advantageously, these quinolylnitrones of formula (I) have a broad-spectrum effect, being efficient in the prevention and treatment of hearing loss regardless of its origin, whether caused by a physical agent, such as noise, or an ototoxic agent such as H2O2.

The present invention relates to a methionine sulfoxide reductase B1 inhibitor and an anticancer composition comprising same. More specifically, the present invention relates to 4-[3-(4-ethylphenyl)-5-(4-hydroxyphenyl) -4,5-dihydro -1 H-pyrazol-1-yl]benzene-1-sulfonamide or 6-chloro-10-(4-ethylphenyl)-4-hydroxypyrimido[4,5-b]quinolin-2(10H)-one, which is a MsrB1 inhibitor, and an anticancer composition comprising same. The MsrB1 inhibitor of the present invention has been confirmed to inhibit differentiation into tumor-friendly M2 macrophages and to suppress tumor growth. In addition, the MsrB1 inhibitor of the present invention was found to exhibit anticancer effects through immune regulation within the tumor microenvironment, and thus can be usefully applied as a composition for cancer treatment.

This invention provides an imine reductase mutant, its preparation method, and its application in the catalytic preparation of dextromethorphan intermediates. The imine reductase mutant is an imine reductase with an amino acid mutation, comprising the amino acid sequence shown in SEQ ID NO:1. The amino acid mutation type includes any one or a combination of at least two of I122T, D212A, or G228R. By introducing a mutation into the imine reductase, this invention significantly improves the enzyme's activity and stereoselectivity, enabling the high-yield synthesis of the dextromethorphan intermediate (S)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline under mild conditions, greatly reducing production costs and making it suitable for industrial production.