136 results about "Quinazolinone" patented technology

The invention discloses a quinazolinone compound as well as a preparation method, a pharmaceutical composition and application thereof, and relates to the technical field of pharmaceutical chemistry. In particular to a quinazolinone compound as shown in a formula I or pharmaceutically acceptable salt, prodrug, stereoisomer, diastereoisomer, enantiomer, tautomer, solvate, salt of solvate, polymorphic substance and isotope labeled compound of the quinazolinone compound. The quinazolinone compound designed and synthesized by the invention can effectively inhibit TAK1 protein activity, achieves an excellent curative effect at a molecular level, and can be applied to preparation of medicines for treating and / or preventing inflammation, chronic fibrosis diseases, hyperproliferative diseases and cardiovascular diseases.

The present invention provides a quinazolinone-fused five-membered heterocyclic derivative with a structure represented by formula (I-A). Experimental results show that the compound provided by the present invention has good inhibitory activity against MAT2A, has inhibitory activity against the proliferation of cancer cells with an MTAP deletion mutation, and can be used for treating and / or preventing MAT2A-related cancer diseases.

Provided herein are quinazolinone compounds for modulating muscle myosin to treat obesity and related disorders such as cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, cancer, and osteoarthritis.

The invention relates to the field of organic chemical synthesis, in particular to a quinazolinone compound synthesized by carbon dioxide and a preparation method of the quinazolinone compound. According to the preparation method for synthesizing the quinazolinone compound from carbon dioxide, carbon dioxide, a 2-aminobenzamide compound and aryl halide are taken as raw materials, and are subjected to a heating reaction in the presence of a palladium metal catalyst, a ligand, a reducing agent, alkali and an organic solvent to generate the quinazolinone compound. The mechanism is as follows: carbon dioxide forms an intermediate A under the conditions of alkali and a reducing agent, aryl halide and the intermediate A form a carbonyl metal compound B under the action of a palladium metal catalyst, and then the carbonyl metal compound B reacts with a 2-aminobenzamide compound under the action of the alkali and the reducing agent to obtain the quinazolinone compound. The catalyst system has universality to various types of 2-aminobenzamide and derivatives and aryl halides thereof, the raw materials are wide in source, cheap and easy to obtain, and the reaction process is simple and controllable.

Small molecule inhibitors of Nav1.8 voltage-gated sodium ion channel, including compounds of formula (I), (II), (III), (IV), and (V) are described. Also described are pharmaceutical compositions containing a compound of formula (I), (II), (III), (IV), and (V) and uses of the compounds and pharmaceutical compositions for inhibiting Nav1.8 voltage-gated sodium channels and treating Nav1.8 mediated diseases, such as pain and pain-associated diseases and cardiovascular diseases, such as atrial fibrillation.

The application discloses a dihydroquinazolinone-containing N-hydroxy amide compound and a preparation method and application thereof, relates to the technical field of medicinal chemistry, and utilizes the splicing principle to design and synthesize dihydroquinazolinone-containing N-hydroxy amide compounds with novel structures, and the compounds are tested in terms of HDAC6 protein affinity and anti-proliferation activity of cervical cancer cell Siha, and the results show that the compounds E1-E5 have better affinity to the HDAC6 protein, the IC 50 values are 4.1-85.4 nM, wherein the affinity of the compound E4 to the HDAC6 protein is higher than that of a positive control SAHA; and the compounds E1-E5 can better inhibit the proliferation of the cervical cancer cell Siha, the IC 50 values are 2.4-9.3 muM, wherein the activity of the compound E4 is the strongest.

This application relates to the field of organic chemical synthesis, specifically to a method for synthesizing quinazolinone compounds from carbon dioxide and its preparation. The method uses carbon dioxide, 2-aminobenzamide compounds, and aryl halides as raw materials, and reacts under heating in the presence of a palladium metal catalyst, a ligand, a reducing agent, a base, and an organic solvent to generate quinazolinone compounds. The mechanism is as follows: carbon dioxide forms intermediate A under alkaline and reducing conditions; the aryl halide reacts with intermediate A under the action of a palladium metal catalyst to form a carbonyl metal compound B, which then reacts with the 2-aminobenzamide compound under the action of an alkaline and reducing agent to obtain the quinazolinone compound. This catalyst system is universally applicable to various types of 2-aminobenzamides and their derivatives, as well as aryl halides; the raw materials are widely available, inexpensive, and readily available; and the reaction process is simple and controllable.

The invention discloses 9-phenyl-10-aryloxy evodiamine quinazolinone with a structural formula shown as a formula 3, wherein Ar is selected from benzyl and substituted benzyl. The invention further discloses a preparation method of the 9-phenyl-10-aryloxy evodiamine quinazolinone. The 9-phenyl-10-aryloxy evodiamine quinazolinone derivative as shown in the formula 3 is prepared by the following steps: (1) taking 10-hydroxyevodiamine (A) as a raw material, and reacting with an arylation reagent (ArX) in the presence of a proper alkali catalyst under proper conditions to obtain 10-aryloxy evodiamine 1; (2) reacting the compound 1 with a bromination reagent under proper conditions to obtain 9-bromo-10-aryloxy evodiamine 2; and (3) reacting the compound 2 with an arylboronic acid reagent under proper conditions to obtain the 9-phenyl-10-aryloxy evodiamine quinazolinone derivative 3. The 9-phenyl-10-aryloxy evodiamine quinazolinone derivative 3 synthesized by the preparation method disclosed by the invention is used for treating liver cancer cells in vitro; the neuroblastoma cells show good anti-cancer activity and can be applied to preparation of corresponding anti-tumor drugs.

The present invention relates to quinazolinones and related compounds which degrade PARP14 and are useful, for example, in the treatment of cancer and inflammatory diseases.

The invention discloses a quinazolinone 5-HT2A receptor antagonist or agonist compound as shown in a formula I, pharmaceutically acceptable salts of the quinazolinone 5-HT2A receptor antagonist or agonist compound as well as a preparation method and medical application of the quinazolinone 5-HT2A receptor antagonist or agonist compound and the pharmaceutically acceptable salts. The quinazolinone 5-HT2A receptor antagonist or agonist compound is a powerful 5-HT2A receptor antagonist and has potential anti-mental disease activity.

The invention belongs to the technical field of preparation of quinazolinone. The invention provides a method for preparing butene substituted quinazoline-4 (3H)-ketone, which is characterized in that a spiro-2, 3-dihydroquinazoline-4 (1H)-ketone compound, sodium bicarbonate, 4DPAIPN and dimethyl sulfoxide are subjected to a reaction together. According to the method provided by the invention, additional addition of a metal catalyst, a ligand and an additional oxidant is not needed, reaction conditions are relatively mild, an operation process is relatively simple and convenient, post-treatment is relatively easy, side reactions possibly caused under high temperature and strong oxidation conditions can be reduced, and potential problems caused by metal residues and use of the oxidant are reduced.

The present invention relates to a new process for the preparation of (3R)—N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide, as well as to a novel intermediate useful for the synthesis of said compound at large scale.

A 2,3-fused quinazolinone derivative, its preparation method, and application are disclosed. A 2,3-quinazolinone derivative was synthesized using a simple method with high yield and low production cost. At a concentration of 5 µM and an LPS concentration of 1 µg / mL, compounds 1e and 1f exhibited superior NO release inhibition compared to the anti-inflammatory drugs indomethacin and evodiamine, while compounds 1g and 1q were comparable to indomethacin, and compounds 1w and 1m were comparable to evodiamine. Compounds 1e, 1f, 1g, 1q, and 1m, which exhibited strong NO release inhibition, exhibited less cytotoxicity against RAW264.7 cells than the anti-inflammatory drugs indomethacin and evodiamine. The derivative exhibited significant anti-inflammatory effects and low toxicity. The derivative can be formulated into various dosage forms of anti-inflammatory drugs, possessing high medical value and broad market prospects.

The present invention relates to dihydroquinazolinone compound, a preparation method therefor, and a use thereof. The dihydroquinazolinone compound has an excellent inhibitory effect on GLUT9, can effectively inhibit GLUT9 activity so as to promote uric acid excretion, thereby achieving a uric acid lowering effect, and can be used for treating diseases related to GLUT9 activity or expression. The dihydroquinazolinone compound or a pharmaceutically acceptable salt thereof has no obvious toxicity to organs, can significantly reduce kidney damage caused by hyperuricemia, and alleviates gout symptoms.

This invention discloses a method for preparing a bis(trifluoromethyl)quinazolinone amide derivative, comprising the following steps: under nitrogen protection, intermediate A is activated using an alkaline reagent, and then an acylation reagent is added to react and obtain the target compound. By innovatively utilizing a precise ratio system of bis(trimethyl)silylamine lithium (LiHMDS) and acetic anhydride, and conducting the reaction under low-temperature conditions, the acylation step can be completed in only 1-5 minutes, significantly shortening the overall process cycle compared to traditional methods and greatly improving production efficiency.

The invention discloses a synthesis method of a 2-position amide substituted quinazolinone derivative, which is characterized in that anthranilamide and pyruvoamide are used as raw materials, under the condition that N, N-dimethylformamide is used as a solvent, iodine is used as a catalyst, and various amide-containing quinazolinone derivatives with different substituent groups are conveniently and quickly prepared. The method is wide in substrate compatibility, mild in reaction condition, easy to operate, simple in post-treatment and suitable for industrial production.

The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP / TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds. The present disclosure furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds as well as to said compositions or preparations for use as a medicine, more preferably for the prevention or treatment of diseases mediated by activity of YAP / TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to processes for the preparation of said compounds.

A compound of general formula (I) and also the stereoisomeric forms, mixtures of stereoisomeric forms or pharmaceutically acceptable salts thereof, and also to the use thereof for the prevention and / or treatment of disorders caused by intracellularly acting toxins using retrograde transport, or by viruses or bacteria using retrograde and / or syntaxin 5-dependent transport to infect cells.

The invention discloses a method for synthesizing 2, 3-disubstituted quinazolinone based on NHC-palladium catalytic oxidative coupling. A methyl anthranilate derivative, a non-tert-butyl isocyanide derivative and an arylboronic acid derivative are taken as substrates, the molar ratio is 0.5: 1.2: 1.0, a reaction is performed for 24 hours in a sealed tube at the temperature of 100 DEG C under the protection of nitrogen in an NHC-palladium catalyst, a copper acetate oxidizing agent and a DMF (Dimethyl Formamide) solvent, and a product is obtained through silica gel column chromatography purification. The method solves the problems of narrow substrate, low atom economy and the like in the prior art, is compatible with electron donating / withdrawing and halogen groups, has the yield of 47-97% and mild conditions, and is suitable for efficient synthesis of active heterocyclic compounds in the field of medicines.

The invention discloses an acylhydrazone compound containing a quinazolinone fragment as well as a preparation method and application thereof, and relates to the technical field of medicinal chemistry, the acylhydrazone compound containing the quinazolinone fragment or pharmaceutically acceptable salt, isomer, hydrate, solvate, crystal form and prodrug of the acylhydrazone compound, and the structural formula of the acylhydrazone compound containing the quinazolinone fragment or pharmaceutically acceptable salt, isomer, hydrate, solvate, crystal form and prodrug of the acylhydrazone compound containing the quinazolinone fragment is shown in the specification. According to the invention, acylhydrazone compounds containing quinazolinone fragments are designed and synthesized by utilizing a splicing principle, the compounds are subjected to anticancer activity test, and the compounds with anticancer activity superior to that of 5-fluorouracil are screened out from the acylhydrazone compounds.

The invention relates to a synthetic method of an indoloquinazolinone compound. The synthetic method comprises the following steps: reacting 2-aminoacetophenone with aryl isocyanate under the catalytic action of a palladium complex to obtain the indoloquinazolinone compound, wherein the palladium complex is an N, N-coordinated palladium complex containing a meta-carborane ligand. The preparation process of the palladium complex comprises the following steps: adding an n-BuLi solution into a meta-carborane solution to carry out a deprotonation reaction, then adding 3-chloromethylpyridine to carry out a nucleophilic substitution reaction, finally adding Pd (OAc) 2 to carry out a coordination reaction to obtain a palladium complex head product, and carrying out post-treatment to obtain the palladium complex product. Compared with the prior art, the method disclosed by the invention has the advantages of good adaptability, high catalytic efficiency, few byproducts, mild reaction conditions, lower cost, easiness in product separation, no generation of a large amount of waste residues and the like.

The invention provides a quinazolinone five-membered heterocyclic derivative with a structure as shown in a formula (I-A). Experimental results show that the compound provided by the invention has good MAT2A inhibitory activity, also has inhibitory activity on proliferation of MTAP deletion mutation cancer cells, and can be used for treating and / or preventing MAT2A-related cancer diseases.

The invention relates to application of a polycyclic quinazolinone compound in resisting plant pathogenic fungi in the technical field of organic synthetic chemistry and agricultural pharmacology, the structural formula of the derivative is shown as I or II, in the structural formula, R is H, 4-OMe, 4-Me, 4-CO2Me, 4-F, 4-CF3, 4-Cl, 4-Br, 2-Br or 2-F, and R is H, 4-OMe, 4-Me, 4-CO2Me, 4-F, 4-CF3, 4-Cl, 4-Br, 2-Br or 2-F; the series of compounds have a certain inhibition effect on plant pathogenic fungi including strawberry botrytis cinerea, fusarium graminearum, rhizoctonia solani and magnaporthe oryzae, and can be applied to plant protection as a bactericide. The preparation method comprises the following steps: by taking N-cyanamide olefin as a raw material and lauroyl peroxide as an oxidizing agent, reacting in a dichloromethane or trichloromethane solvent at 80-120 DEG C to obtain the polycyclic quinazolinone compound with antibacterial activity. The preparation method is simple to operate, green and efficient.

The application belongs to the field of chemical industry, and particularly relates to a synthesis method of a substituted pyrazoloquinazoline derivative. The method provided by the application comprises sequentially preparing 2-chloro-5,6,7,8-tetrahydroquinazoline, 2-chloro-6,7-dihydroquinazolin-8(5H)-ketoxime, 2-chloro-6,7-dihydroquinazolin-8(5H)-ketone, 2-(2-methoxy-8-oxo-5,6,7,8-tetrahydroquinazolin-7-yl)-2-oxoacetic acid methyl ester and 1-(2-hydroxyethyl)-8-methoxy-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylic acid methyl ester, and finally obtaining 1-(2-hydroxyethyl)-8-((5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide. By using the method of the application, three reaction steps are reduced, the total yield is increased by nearly one time, and the method is far higher than the original process route; and the application of dangerous reagents such as hydrazine hydrate and iodine is avoided, and the method is easy to scale up.

The invention discloses 9-phenyl-10-cyclopropyl methoxy evodiamine quinazolinone with a structural formula as shown in a formula 3, and 9-phenyl-10-cyclopropyl methoxy evodiamine quinazolinone derivatives as shown in the formula 3. The preparation method comprises the following steps: (1) taking 10-hydroxy evodiamine (A) as a raw material; reacting with bromomethyl cyclopropane in the presence of a proper alkali catalyst under proper conditions to obtain 10-cyclopropyl methoxy evodiamine 1; (2) reacting the compound 1 with a bromination reagent under proper conditions to obtain 9-bromo-10-cyclopropyl methoxy evodiamine 2; and (3) reacting the compound 2 with an arylboronic acid reagent under proper conditions to obtain the 9-phenyl-10-cyclopropyl methoxy evodiamine quinazolinone derivative 3. The 9-phenyl-10-cyclopropyl methoxyl evodiamine quinazolinone derivative synthesized by the invention has the advantages that the 9-phenyl-10-cyclopropyl methoxyl evodiamine quinazolinone derivative is used for treating liver cancer cells in vitro; the neuroblastoma cells show good anti-cancer activity and can be applied to preparation of corresponding anti-tumor drugs.

The application discloses a 2,3-dihydroquinazolinone compound and a preparation method and application thereof. A substituted 3-(but-3-en-1-yl)quinazolin-4(3H)-one of formula 1 is subjected to chemical reaction under reaction conditions to obtain a 2,3-dihydroquinazolinone compound with different substituents of formula 2; or a substituted N-cyano-N-[(1-vinyl-2-yl)phenyl]benzamide of formula 3 is subjected to chemical reaction under reaction conditions to obtain a 2,3-dihydroquinazolinone compound with different substituents of formula 4; the disclosed synthesis method is simple, safe and low in reaction cost. Moreover, the 2,3-dihydroquinazolinone compound prepared by the method has excellent inhibitory activity on tumor cells.

This invention discloses a visible light-induced method for synthesizing α,β-unsaturated acetylide amides, belonging to the field of organic synthesis. The invention constructs a visible light-responsive aromatization-driven carbamoyl radical precursor—a dihydroquinazolinone derivative precursor containing a carbamoyl segment. Under direct visible light irradiation, a single-electron process is triggered, leading to C-C bond cleavage and aromatization, thereby efficiently releasing a carbamoyl radical in situ. Subsequently, this radical undergoes selective acetylation transfer and coupling with an acetylation-based high-valent iodine reagent, achieving the rapid construction of the target α,β-unsaturated acetylide amide. This process can be completed via a one-pot pathway of "visible light direct-driven—radical generation—acetylation transfer / coupling," avoiding the introduction of additional photocatalysts, making the reaction system simpler, the cost more controllable, and the post-processing more convenient.

The invention belongs to the technical field of medical compounds, and particularly relates to a quinazolinone dodecylamine derivative and application thereof, and the structure of the dodecylamine derivative is shown in the specification. X is NH; l1 represents (CH2) n, wherein n is from 0 to 4; h represents an unsubstituted or substituted aromatic ring, and the substitution is halogen substitution; l2 represents (CH2) n, wherein n = 0-4; r1 represents a substituted amino group or a nitrogen-containing heterocyclic ring; according to the invention, the anti-tumor effect is effectively improved.

The present invention relates to an application of a Ru-Pt alloy catalyst in catalyzing the acceptor-free dehydrogenation of alcohols to synthesize quinazolinone compounds. The Ru-Pt alloy catalyst includes a carbon black support and active components ruthenium and platinum supported on the carbon black support. In the method for synthesizing quinazolinone compounds by acceptor-free dehydrogenation of alcohols, the present invention adopts the Ru-Pt alloy catalyst. The Ru-Pt alloy catalyst can efficiently catalyze the reaction of aminobenzamide compounds with relatively low-equivalent alcohols without adding additives such as acid-base additives, oxidants, or hydrogen acceptors, thereby achieving a high yield of quinazolinone compounds. Furthermore, the Ru-Pt alloy catalyst can achieve good cycle performance by only undergoing a simple washing and drying process without requiring activation treatments such as oxidation or reduction.

Provided is a 2-heteroaryl aminoquinazolinone derivative, which is a compound represented by formula (1):or a pharmaceutically acceptable salt thereof wherein X1 represents CR1 or N, X2 represents CR2 or N, X3 represents CR3 or N, X4 represents CR4 or N, Y represents optionally substituted C1-6 alkyl, an optionally substituted C3-10 alicyclic group, an optionally substituted 4- to 10-membered nitrogen-containing non-aryl heterocycle, optionally substituted C6-10 aryl, or optionally substituted 5- to 10-membered heteroaryl, Z represents optionally substituted 6- to 10-membered heteroaryl, and R1, R2, R3, and R4 each independently represent a hydrogen atom, halogen, cyano, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkoxy, or the like.