355 results about "Isoquinoline" patented technology

The present application relates to the technical field of small molecule drugs, in particular to a isoquinoline drug and its application in improving or treating digestive tract tumors, and aims to provide a compound, a pharmaceutical composition containing the compound and its application in treating colorectal cancer and gastric cancer, and provides a 3,13-position substituted berberine derivative, the drug itself has less toxicity and does not affect the growth of normal human cells, and has a good application prospect in the development of novel antitumor drugs, especially in the development of anti-digestive tract tumor drugs.

Disclosed are a series of isoquinolone derivatives as ROCK protein kinase inhibitors and uses thereof in preparing medicaments for ROCK protein kinase inhibitor-related glaucoma or ocular hypertension diseases. Specially, disclosed are a compound of formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof.

The invention discloses a fluorescent probe as well as a preparation method and application thereof. The invention provides a series of fluorescent probes with novel structures, and the fluorescent probes take 2-(isoquinoline-1-yl) pyrrole boron difluoride as fluorophores, so that the fluorescence quantum yield of the probes is improved, the detection resolution of nitric oxide is increased, and the detection sensitivity is improved. The fluorescent probe disclosed by the invention has the characteristics of large Stokes displacement, high fluorescence quantum yield, good selectivity and short response time.

The invention relates to a fluorescent probe for hypochlorous acid detection and a preparation method and application thereof, the chemical name of the fluorescent probe for hypochlorous acid detection is 5-butyl-10, 10-difluoro-9-(4-(methylthio) phenyl)-5-hydro-4H, 10H-9 lambda 4, 10 lambda 4-benzo [de] [1, 3, 2] oxazaboraza [6, 5-g] isoquinoline-4, 6-diketone, and the structural formula of the fluorescent probe for hypochlorous acid detection is as shown in the following formula I. The invention further discloses a preparation method of the fluorescent probe for hypochlorous acid detection. According to the fluorescent probe for hypochlorous acid detection, N-butyl-3-aldehyde-4-hydroxy-1, 8-naphthalimide and (E)-2-butyl-6-hydroxy-5-(((4-(methylthio) phenyl) imino) methyl)-1H-benzo [de] isoquinoline-1, 3 (2H)-diketone are used as raw materials, and the fluorescent probe can be used for detecting hypochlorous acid. Compared with the prior art, the fluorescent probe for hypochlorous acid detection is simple and convenient in synthesis method, simple and easily available in raw materials, good in hypochlorous acid selectivity, relatively high in sensitivity and large in Stokes shift, and has a very good application prospect in hypochlorous acid detection.

Provided in the present invention are a compound as represented by formula (I), or a pharmaceutically acceptable salt, a tautomer, a geometrical isomer, an optical isomer, a solvate or an isotopic derivative thereof, and the use thereof. The compound of the present invention has a significant inhibitory activity on PRMT5, has a significant inhibitory effect on tumor cells and in vivo tumor models, also has a good administration performance, and has clinical application potential for preventing and / or treating diseases which are at least partially mediated by PRMT5.

The invention discloses a cephalotaxus hainanensis Ch2OGD1 gene and application thereof, and belongs to the technical field of gene engineering. The Ch2OGD1 gene is used for coding a 2-oxoglutaric acid dependent dioxygenase (2OGD) type Pictet-Spengler enzyme, and the Pictet-Spengler enzyme is used for coding a Pictet-Spengler enzyme. Through a tobacco transient expression system and in-vitro enzyme activity determination, the Ch2OGD1 is proved to be capable of specifically catalyzing the condensation of dopamine and 4-hydroxyphenylpropanal to generate 1-phenethyl isoquinoline. The invention provides a directional preparation method of 1-phenethyl isoquinoline based on the Ch2OGD1 gene, provides a key enzyme element for biosynthesis of a cephalotaxine alkaloid precursor compound, and provides a technical basis for expanding the application of the gene in plant genetic engineering. And a potential technical path is provided for relieving the problem of resource shortage of cephalotaxine alkaloids.

The invention relates to the technical field of pesticides, in particular to a hydrazide derivative containing a 3, 4-dihydroisoquinoline structure, a preparation method and application. The hydrazide derivative containing the 3, 4-dihydroisoquinoline structure is a compound as shown in a formula (I), or a stereoisomer, a tautomer, an isotope derivative and a pesticide acceptable salt thereof. The hydrazide derivative containing the 3, 4-dihydroisoquinoline structure has broad-spectrum inhibitory activity on phytopathogens such as plant pathogenic fungi, especially has excellent inhibitory activity on basidiomycota and ascomycomycota pathogenic fungi such as gaeumannomyces graminis, physalospora piricola, sclerotinia sclerotiorum, botrytis cinerea and rhizoctonia solani, and has broad-spectrum inhibitory activity. The bactericide is expected to be developed into a novel green bactericide which is efficient, safe, economical and environment-friendly.

The application discloses a preparation method of enciferstat bulk drug and belongs to the field of drug synthesis. 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (SM) is used as a raw material, and the raw material is reacted with cyclohexylamine under alkaline conditions, and the reaction is washed with water, dried, and concentrated to obtain an intermediate I; the intermediate I is reacted with urea under pressurized heating conditions to prepare an enciferstat drug molecule, the two-step yield is more than 67%, and the purity is more than 99%, the method has a simple operation process, the product is easy to purify, the yield is high, the product purity is high, and a new method for preparing enciferstat bulk drug is provided.

The invention provides a purification method of a naphthalimide high-purity electronic-grade photoacid generator. The method solves the problem that photo-acid cannot be purified by traditional recrystallization or directly through ion exchange columns and other methods. The method comprises the following steps: firstly synthesizing and preparing 1, 3-diketone-2-hydroxy-6-(1-hexyne) benzisoquinoline, then reacting with triethylamine and trifluoromethylsulfonyl chloride to generate a crude product 1, 3-diketone-2-(1, 1, 1-trifluoromethyl) methanesulfonic ester-6-(1-hexyne) benzisoquinoline, removing impurities from normal hexane to obtain a pure product, sublimating the material into a gas phase by using a quartz vacuum sublimation instrument, and purifying to obtain the 1, 3-diketone-2-(1, 1, 1-trifluoromethyl) methanesulfonic ester-6-(1-hexyne) benzisoquinoline. And then passing through Pure MTS9500 amino phosphonic acid type chelating resin, and finally cooling in a quartz tube to obtain the high-purity electronic-grade photoacid generator. According to the invention, the stability is high, the metal ion content is low, the purification process is convenient to process, the product is used as a photoresist-level core main material, the product is widely applied in the fields of semiconductor photoresist, other imaging systems, photocureable coatings and the like, the market scale is continuously expanded, and the product is an indispensable key material in semiconductor manufacturing and other related fields.

This invention provides an aminoisoquinoline derivative and its application in the preparation of antiviral drugs. The invention reveals that the aminoisoquinoline derivative exhibits significant inhibitory effects against various RNA and DNA viruses, demonstrating broad-spectrum activity. This small-molecule inhibitor has low toxicity and does not affect the normal growth of host cells. It shows good antiviral efficacy even at low concentrations. The results of this invention indicate that the compound has the potential to be used in the preparation of antiviral drugs and has promising clinical application prospects.

The invention discloses purslane isoquinoline alkaloid as well as a preparation method and application thereof. The purslane isoquinoline alkaloid is shown as a formula 1 or a formula 2, has GLP-1 receptor agonistic activity and can be used for preparing medicines and health-care foods for preventing and treating diabetes mellitus.

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 application relates to the technical field of organic synthesis, and particularly relates to a method for preparing (+)-crispine A by means of biological enzyme resolution. First, 6,7-dimethoxy-3,4-dihydroisoquinoline-2-oxide is subjected to 1,3-dipolar cycloaddition with allyl alcohol to obtain a first compound; then the first compound is added into a sulfonylation reagent and zinc powder to obtain a racemate second compound through a three-step continuous series reaction of primary alcohol sulfonylation, nitrogen-oxygen bond cleavage and ring formation; then the second compound is mixed with vinyl acetate and biological enzyme, and chiral resolution is carried out under the action of the biological enzyme to obtain a third compound with right-handed optical rotation and a fourth compound with left-handed optical rotation; finally, the third compound is mixed with an alkaline reagent and a sulfonylation reagent, and then secondary alcohol sulfonylation is carried out to obtain a fifth compound with right-handed optical rotation; the fifth compound is mixed with a deoxidizing reagent to carry out deoxidation reaction, and (+)-crispine A is prepared. The method is simple, green and environmentally friendly, and can be produced in large quantities.

The present invention provides, in part, novel small molecule inhibitors of PHD, having a structure according to Formula (I), and sub-formulas thereof: Formula (I) or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for treatment or prevention of diseases including heart (e.g. ischemic heart disease, congestive heart failure, and valvular heart disease), lung (e.g., lung inflammation, pneumonia, acute lung injury, pulmonary hypertension, pulmonary fibrosis, and chronic obstructive pulmonary disease), respiratory (e.g.,respiratory infection, acute respiratory distress syndrome), liver (e.g. acute liver failure and liver fibrosis and cirrhosis), and kidney (e.g. acute kidney injury and chronic kidney disease) disease, inflammatory bowel disease (IBD), ischemic reperfusion injury (e.g., stroke), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and white matter injury (WMI).

The invention belongs to the technical field of organic synthesis, and particularly relates to a 3-fluoroisoquinoline-4-alcohol compound and a preparation method and application thereof.The preparation method comprises the steps that substituted 2-azido-2-fluoro-2, 3-dihydro-1H-indene-1-ketone reacts with a solvent; adding an extracting agent for extraction, taking an organic phase, drying, filtering and concentrating to obtain a crude product; and purifying to obtain the 3-fluoroisoquinoline-4-alcohol compound. The solvent is prepared from dimethyl sulfoxide, N, N-dimethyl formamide, acetonitrile, isopropanol, tetrahydrofuran, 1, 4-dioxane, dichloromethane and chloroform. Compared with the prior art, the invention solves the problems that the synthesis of isoquinoline compounds in the prior art needs multi-step reaction, the reaction conditions are harsh, and the tolerance of functional groups is poor. According to the scheme, the 3-fluoroisoquinoline-4-alcohol compound is obtained through one-step chemical reaction, and the method has the advantages that raw materials are simple and easy to obtain, the substrate range is wide, the reaction is mild, the yield is high and the like.

The invention discloses a preparation method of a covalent organic framework photocatalyst for photocatalytic reduction of CO2, which comprises the following steps: adding 4, 4 ', 4' '-(1, 3, 5-triazine-2, 4, 6-triyl) triphenylamine and 2, 5-dibromobenzene-1, 2, 4, 5-tetracarboxylic dianhydride into a reaction kettle, then adding 1-hydroxy-3-methylbenzene and isoquinoline, and uniformly mixing; and carrying out microwave heating on the reaction kettle, cooling to room temperature, filtering, collecting precipitate, washing, and then carrying out Soxhlet extraction and vacuum drying to obtain the covalent organic framework photocatalyst. A surface halogen atom modification strategy is designed and used for regulating and controlling electron distribution and light capture capacity of a donor-acceptor (D-A) in TzPm-COF, and results show that the strategy can effectively improve photocatalytic activity and selectivity of reduction of CO2 into CO, and can be applied to preparation of the TzPm-COF catalyst. A reasonable design strategy is provided for developing a functional modified COFs material for efficiently and selectively photocatalytic CO2 reduction.

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 application relates to the technical field of electronic materials, and discloses a fluorinated iridium complex, a preparation method and application thereof, and an organic photoelectric device. The fluorinated iridium complex has a structure shown in formula (I): R 1 is a C1-C13 alkyl substituent, R 2 is a C1-C13 alkyl substituent, and the substitution sites are the meta and para positions of a carbon atom of an isoquinoline phenyl linkage, X is an independently existing hydrogen atom, a fluorine atom or an alkyl substituent, wherein the alkyl substituent is a deuterated, partially deuterated or aryl-substituted alkyl group; the fluorinated iridium complex realizes high-efficiency supersaturation deep red light as a red phosphor material in an organic light-emitting device.

The present invention discloses a process for preparing compound of Lifitegrast of Formula (I) or a salt thereof. Briefly, The present invention discloses a process for the preparation of Lifitegrast of Formula I from alkyl (S)-2-(5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6- carboxamido)-3-(3 (methylsulfonyl)phenyl)propanoate a compound of Formula V via 5 transesterification of Phenyl (S)-2-(5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6- carboxamido)-3-(3)(methylsulfonyl)phenyl) propanoate of Formula IV.

The present invention provides boron-containing isoquinoline compounds as protein kinase-modulating compounds. These compounds are useful as neuroprotective and neuro-regenerative agents for the amelioration of glaucoma and other ocular neuropathies.

The application discloses a synthesis method of aromatic aldehyde, comprising the following steps: under inert atmosphere, a compound shown in formula I and a compound shown in formula II are reacted in an organic solvent containing a photocatalyst, a nickel catalyst, a ligand, a base and water under blue light irradiation to obtain aromatic aldehyde shown in formula III; formula I, formula II and formula III are structures as follows, ring A is selected from benzene, pyridine, thiophene, furan, pyridazine, indazole, indole, isoquinoline, quinoline, naphthalene, benzothiophene, dibenzofuran or dibenzothiophene; the application generates formyl radicals under the nickel synergistic photo-oxidation and reduction catalytic condition, and the formylation of bromobenzene and its derivatives is realized in a simple and efficient one-pot way, aromatic aldehyde is constructed, and the reaction has the characteristics of cheap and easily available raw materials, mild reaction conditions, controllable synthesis process, high separation yield / yield, green environmental protection, wide substrate applicability and the like.

The present invention provides novel isoquinolinone compounds that are inhibitors of mitochondrial RNA polymerase for treating various diseases such as cancer and others associated with metabolic disorders and mitochondnal dysfunction.

The application belongs to the field of pharmaceutical chemistry and specifically relates to a preparation method of 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline, which comprises the following steps: adding a reducing agent in an alkaline aqueous solution, adding a cosolvent under nitrogen protection, controlling the temperature at 10-30 DEG C, slowly adding an aqueous solution of compound 2, and stirring to react, thereby obtaining the product directly. In the application, after compound 2 is prepared, the post-reaction liquid is not concentrated, and the product is extracted with water, thereby solving the problem of unstable product concentration. In the reduction reaction from compound 2 to compound 3, the reducing agent is added in the aqueous solution of sodium hydroxide at one time, the solvent is added to assist dissolution, and then the aqueous solution of compound 2 is added to perform the reduction reaction, the process is mild, the cumbersome batch addition of the reducing agent is avoided, the reaction time is short, the energy consumption is low, the post-treatment is mild, and the obtained product has the advantages of high yield and high purity.

The present invention relates to isoquinolines as HPK1 inhibitors. Isoquinoline compounds and their use as HPK1 (hematopoietic kinase 1) inhibitors are described. The compounds are useful in treating HPK1 dependent disorders and in enhancing immune responses. Methods of inhibiting HPK1, methods of treating HPK1 dependent disorders, methods for enhancing immune responses, and methods for making the isoquinoline compounds are also described.

The application discloses a method for synthesizing 1,7-dibromoisoquinoline, which comprises the following steps: under the condition of inert gas protection, isoquinoline is reacted with bromine in an aprotic solvent at a reaction temperature of-60 DEG C to-90 DEG C under the action of butyl lithium to obtain 1,7-dibromoisoquinoline. The application innovatively makes isoquinoline react with bromine under the action of butyl lithium to obtain 1,7-dibromoisoquinoline, the raw material used is low in price, the method has the characteristics of short reaction steps, short reaction time, high yield and the like, and is suitable for large-scale production.

Applicant discloses methods and compositions for treating a patient suffering from amyotrophic lateral sclerosis (ALS) comprising administration of a heteroaryl ketone fused azadecalin compound. In embodiments, the heteroaryl ketone fused azadecalin compound is dazucorilant: (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl) sulfonyl)-4, 4a, 5,6,7,8-hexahydro-1-H-pyrazolo[3,4-g]isoquinolin-4a-yl) (pyridin-2-yl)methanone, having the chemical structure illustrated asSuitable doses include daily administration of 150 milligrams and 300 milligrams of dazucorilant. Suitable doses include daily administration of dazucorilant with food, or with water, or with food and water. Daily administration of dazucorilant is effective to increase dazucorilant exposure up to about 2-fold when continued for seven days or more. Administration of such a heteroaryl ketone fused azadecalin compound may comprise oral administration, enteral administration, or other administration. Pharmaceutical compositions comprising dazucorilant are useful in the treatment of patients suffering from ALS. Suitable pharmaceutical compositions comprising dazucorilant include, e.g., pharmaceutical compositions for oral administration and pharmaceutical compositions for enteral administration.

The invention provides a tetrahydroisoquinoline derivative and application thereof. Specifically, the invention relates to a compound as shown in a formula (I), or an isotope variant, a tautomer, a stereoisomer, a prodrug, a polymorphic form, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt thereof. The invention also provides a pharmaceutical composition containing the compound, and an effect of the compound in prevention and treatment of diseases related to the central nervous system.

The present invention relates to compositions comprising 4-({(4-cyclopropylisoquinolin-3-yl)[4- (trifluoromethoxy)benzyl] amino }sulfonyl)benzoic acid (elismetrep; MT-8554), or a pharmaceutically acceptable salt thereof, for treating or preventing pain, particularly migraine or a trigeminal pain disease or condition such as medication overuse headache, cluster headache, general headache, trigeminal neuralgia, trigeminal neuropathy, trigeminal autonomic cephalalgia, orofacial pain, and dental pain.

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.