524 results about "Pyridazine" patented technology

The compounds represented by formula (I) of this invention exhibit excellent activity against a variety of pests and mites in agriculture or other fields. Furthermore, these compounds achieve good control effects at very low doses, and therefore can be used to prepare insecticides and / or acaricides.

Methods for treating prostate cancer, including advanced prostate cancer, in a subject in need thereof, include administering once-daily to the subject, at least 80 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof. Another method includes: administering once-daily to the subject in need thereof, an oral load dose formulation having from 240 mg to 480 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof, and thereafter administering once-daily to the subject, an oral maintenance dose formulation having 80 mg to 160 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof.

The present application relates to a various novel crystalline forms of 2- [3,5-dichloro -4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy) phenyl]-3,5- dioxo- 2,3,4,5-tetrahydro [1,2,4] triazine-6-carbonitrile represented by the following structural formula-1, which is referred to as Resmetirom. The present application also relates to process for the preparation of various novel crystalline polymorphic forms of compound of formula-1.

Stable and bioavailable formulations and dosage forms comprising a dispersion (e.g., spray-dried dispersion) of solid amorphous 6-(cyclopropancamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (Formula (I): BMS-986165) in a solid polymer matrix are provided for the treatment of auto-immune and auto-inflammatory diseases such as an inflammatory bowel disease (IBD) and psoriasis.

The present invention relates to solid forms of the poly(ADP-ribose) polymerase 7 (PARP7) inhibitor 5-[[(2S)-1-(3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl]amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, and salts thereof, including methods of preparation thereof, where the inhibitor is useful in the treatment of cancer.

A novel additive, an electrolyte, and a lithium ion battery, relating to the technical field of lithium ion batteries. The electrolyte comprises a lithium salt and a non-aqueous solvent for dissolving the lithium salt, the electrolyte further comprises an electrolyte additive, the electrolyte additive comprises a positive electrode film-forming additive and a negative electrode film-forming additive, and the electrolyte additive further comprises a fluoro isocyanate-based pyridazine organic compound. The additive can absorb moisture and hydrofluoric acid in the electrolyte, reduce the dissolution of transition metals, improve the thermal stability of lithium hexafluorophosphate, and maintains the stability of a ternary material under high voltage; a sulfuric acid group on the novel additive can be oxidized by oxygen at a positive electrode, so that the oxygen generated when an LFO lithium supplementing agent is activated is absorbed, the capacity exertion, high temperature cycle and high temperature storage of the LFO lithium supplementing agent are significantly improved, and the DCIR of the battery will not obviously increase, thereby improving the stability of the battery.

Described herein are crystalline forms of the MAGL inhibitor 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyridazin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate.

The present invention provides a production method of a thienopyrimidine derivative or a salt thereof which has a gonadotropin releasing hormone (GnRH) antagonistic action with high quality in high yield. The present invention provides a method of producing a thienopyrimidine derivative, which comprises reacting 6-(4-aminophenyl)-1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl) thieno[2,3-d]pyrimidine-2,4 (1H,3H)-dione or salt thereof, 1,1′-carbonyldiimidazole or a salt thereof and methoxyamine or a salt thereof, and the like.

Methods for treating prostate cancer, including advanced prostate cancer, in a subject in need thereof, include administering once-daily to the subject, at least 80 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof. Another method includes: administering once-daily to the subject in need thereof, an oral load dose formulation having from 240 mg to 480 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof, and thereafter administering once-daily to the subject, an oral maintenance dose formulation having 80 mg to 160 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof.

The invention discloses a preparation method of 3, 6-dichloropyridazine, and belongs to the technical field of chemistry. According to the method, 3, 6-dihydroxypyridazine is used as a raw material, an organic solvent and triphenylphosphine oxide are combined to form a dichlorotriphenylphosphine intermediate state which is used as a chlorinating agent, dihydroxyl is substituted to generate 3, 6-dichloropyridazine, triphenylphosphine oxide and solid light are used as raw materials, heating reaction is performed to prepare 3, 6-dichloropyridazine, meanwhile, a one-pot method can be adopted in the two-step reaction, and operation is easy and convenient. The novel preparation method for synthesizing 3, 6-dichloropyridazine provided by the invention has the advantages of low raw material cost, high yield, high gas phase purity and no pollution, is suitable for industrial production, can meet industrial requirements, provides a new idea for later preparation of 3, 6-dichloropyridazine, has the remarkable advantages of high gas phase purity and high yield, and is suitable for industrial production. Wide application prospects are realized.

The present disclosure relates to heterocyclyl pyridazine compounds, processes and intermediates for their preparation as well as the uses thereof for controlling phytopathogenic microorganisms, such as phytopathogenic fungi.

The invention discloses a preparation method and application of a nitrogen-containing heterocyclic porous covalent organic framework material. The preparation method comprises the following steps: mixing trialdehyde phloroglucinol and a nitrogen heterocyclic ring-containing monomer according to a certain mass ratio, adding an organic catalyst and a mixed solvent, degassing, sealing, carrying out solvothermal reaction synthesis, washing with a polar solvent, carrying out Soxhlet extraction and purification, and drying to obtain the nitrogen heterocyclic ring-containing porous covalent organic framework material. According to the method, a pyridazine unit and trialdehyde phloroglucinol are used as monomers to construct a COF skeleton of a nitrogen heterocyclic ring, an asymmetric pi-conjugated structure is formed, efficient electron-hole space separation is achieved, active site charge distribution is optimized through the electron-rich characteristic of the pyridazine unit, and the oxygen molecule adsorption and activation capacity is enhanced. The method adopts a green solvent, is mild in reaction condition, avoids the use of toxic reagents, is green and environment-friendly, and provides a new way for photocatalytic synthesis of hydrogen peroxide.

Substituted pyridazinone compounds, conjugates, and pharmaceutical compositions for use in the treatment of neuromuscular diseases, such as Duchenne Muscular Dystrophy (DMD), are disclosed herein. The disclosed compounds are useful, among other things, in the treating of DMD and modulating inflammatory inhibitors IL-1, IL-6 or TNF-α.

The present invention relates to a compound of formula (I) wherein R1 is a hydrogen atom, halogen or -(C1-C2)alkyl, R2 is -halo(C1-C2)alkoxy, and R3 and R4 form together with N to which they are attached an optionally substituted 5-7 membered monocyclic heterocycloalkyl ring or an optionally substituted 8-11 membered bicyclic heterocycloalkyl ring. The present invention also relates to a medicament and a pharmaceutical composition comprising said compound of formula (I), as well as their therapeutic uses, in particular as inhibitor of NOD-like receptor protein 3 inflammasome for preventing and / or treating Parkinson's disease, frontotemporal Dementia, Multiple System Atrophy, Alzheimer's disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis or brain injury.

Provided herein are crystalline salt and free base forms and amorphous forms of a compound having the following formula (I): (I) Compound 1. Also provided are pharmaceutical compositions comprising such crystalline and amorphous forms, processes for their manufacture and their use for the treatment of various conditions such as hemolytic anemia, sickle cell disease and MDS (very low risk MDS, low risk MDS, lower risk MDS and / or moderate risk MDS).

The invention belongs to the technical field of chemical synthesis, and particularly relates to a difluoroalkylated tetrahydropyridazine compound and a preparation method thereof. The preparation method of the difluoroalkylated tetrahydropyridazine compound comprises the following steps: by taking an acethydrazide compound and a difluoroalkyl compound as reaction raw materials, mixing the reaction raw materials, a photosensitizer, reaction alkali and a solvent under a nitrogen condition, and reacting under blue light to obtain the difluoroalkylated tetrahydropyridazine compound. A difluoroalkyl compound is reduced by a photosensitizer to generate a difluoroalkyl free radical, and the difluoroalkyl free radical and an acethydrazide compound are subjected to an addition reaction to obtain the difluoroalkylated tetrahydropyridazine compound. The method does not need to additionally add a metal catalyst or an oxidizing agent or a reducing agent, and is simple to operate, mild in reaction condition, wide in substrate universality, green and environment-friendly.

To provide a compound superior in an ATX inhibitory action and useful for the prophylaxis or treatment of a disease involving ATX.SOLUTION: The invention provides a carboxylic acid compound represented by the general formula (1), or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

The present invention relates to a process for the preparation of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, where: Ring B is a monocyclic aromatic group; the present invention relates to a halogen-containing compound optionally substituted by one or more substituents selected from the group consisting of halogen, CN, OH, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, O-cycloalkyl, alkoxy, haloalkoxy, heterocycloalkyl, O-heterocycloalkyl, aryl, heteroaryl, O-aryl, NHCO-alkenyl, NHCO-aryl,-(CH2) q-O-heteroaryl, CONH-aryl, aryloxy-alkyl, O-aralkyl, and CO2-alkyl, wherein the aryl, heteroaryl, heterocycloalkyl, O-cycloalkyl, NHCO-aryl,-(CH2) q-O-heteroaryl, CONH-aryl, aryloxy-alkyl, O-aralkyl, and O-aryl groups are each optionally further independently selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, NHCO-alkyl, NR < 13 > R < 13 > ', SO2-alkyl, CN, hydroxyalkyl, CONR < 14 > R < 14 >', alkyl-NR < 15 > R < 15 > ', heterocycloalkyl, alkyl-heterocycloalkyl, alkyl-cycloalkyl, wherein, in the latter group, the cycloalkyl is optionally further substituted by one or more halogen, haloalkyl, alkyl or alkoxy groups, and wherein, in the latter group, the cycloalkyl is optionally further substituted by one or more halogen, haloalkyl, alkyl or alkoxy groups, and wherein, in the latter group, the alkyl is optionally further substituted by one or more halogen, haloalkyl, alkyl or alkoxy groups; m is an integer from 0 to 3; p and q are each independently 0 to 3; y is CR10R10 ', wherein R10 and R10' are each independently selected from the group consisting of H, F, alkyl, and haloalkyl; ra and Rb are each independently selected from H and alkyl; r6 is selected from H, alkyl, cycloalkyl and hydroxyalkyl; the present invention relates to a process for the preparation of a compound of formula (I) wherein B is as defined above, and R13, R13 ', R14, R14', R15, R15 ', and R16 are each independently selected from H, alkyl, haloalkyl, and alkoxyalkyl, comprising the steps of: (i) treating a compound of formula (IV) with a compound of formula (V) to form a compound of formula (III) wherein B in formula (IV) is as defined above, R21 in formula (V) is phenyl optionally substituted by 1 to 5 fluorine atoms; and (ii) treating the compound of formula (III) with a compound of formula (II) in which Y, Ra, Rb and R6 are as described above, or a pharmaceutically acceptable salt thereof, to form a compound of formula (I). Other aspects of the invention also relate to intermediates useful in said processes.

The present application relates to a kind of thieno [2, 3-c] pyridazine derivatives, and its isotope form, stereoisomer, tautomer, cis-trans isomer, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, hydrate, prodrug and polymorph, these compounds can be used as cholinergic M4 receptor positive allosteric modulator, it has good application prospect in preparation for preventing and / or treating the drug for the disease related to abnormal muscarinic acetylcholine receptor.

The present disclosure relates to solid state forms of Compound (1) freebase. The present disclosure also relates to processes for the preparation of the solid state forms, the pharmaceutical compositions comprising the forms, and the use thereof, e.g., in the treatment and prevention of disorders in which NLRP3 activity is implicated.

The present invention is directed to morphic forms, co-crystals, salts, and amorphous solid dispersions of 2-(3,5-dichloro-4-((5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile.

The application discloses a method for regionally selective C3-H alkyne of triazolopyridazine compounds, and belongs to the field of organic synthesis. The method uses triazolopyridazine and high-valence iodine (III) alkyne reagent as raw materials, and a double catalytic system composed of Ph3PAuNTf2 (5 mol%), AgOTf (5 mol%) and 1,10-phenanthroline (20 mol%) in dichloromethane, and after reaction at 50 DEG C, the C3 alkyne product is obtained through purification. The method solves the problems of catalyst deactivation and poor selectivity caused by nitrogen-rich heterocyclic rings through gold / silver synergistic catalysis, and realizes precise functionalization of the C3 position. The reaction condition is mild, the substrate is widely applicable (R¹ contains various aryl groups and heteroaryl groups, and R² is compatible with different substituted aryl groups), the yield is 60% to 95%, the step is economical, and the method is suitable for large-scale preparation.

The present invention provides a compound having inhibitory activity against a Mas-related G protein-coupled receptor X2. The present invention provides a compound having the following structural formula or the like, or a pharmaceutically acceptable salt thereof.

Disclosed in the present invention are a method for synthesizing deucravacitinib and intermediates thereof. An intermediate 2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)aniline is prepared by subjecting 2,3-dichloronitrobenzene to an etherification reaction and a cyanation reaction to prepare 2-methoxy-3-nitrobenzonitrile; then reacting 2-methoxy-3-nitrobenzonitrile with ammonium chloride under the action of an alkali to generate 3-(2-methoxy-3-nitrophenyl)-1-methyl-1H-1,2,4-triazole; and finally, carrying out a catalytic reduction reaction to obtain the target product. Another intermediate N-(5-bromo-6-cyanopyrazin-3-yl)cyclopropanecarboxamide is prepared by subjecting 3-amino-6-chloropyridazine to a bromination reaction to prepare 3-amino-4-bromo-6-chloropyridazine, then reacting 3-amino-4-bromo-6-chloropyridazine with sodium nitrite under low-temperature condition and in the presence of an acid to generate a diazonium salt, and then adding a cyanate reagent to generate 4-bromo-6-chloro-3-cyanopyridazine; and finally carrying out a substitution reaction to obtain a target product (I). Deucravacitinib is obtained by subjecting these intermediates to a Buchwald-Hartwig coupling reaction, carrying out nitrile hydrolysis, and carrying out condensation.

A compound useful as an active ingredient in a pharmaceutical composition for the treatment of cancer related to the activation of immune cells or cancer resistant to treatment with anti-PD-1 / anti-PD-L1 antibodies is provided. The inventors hereof have conducted studies on a compound useful as an active ingredient in a pharmaceutical composition for the treatment of cancer related to the activation of immune cells or cancer resistant to treatment with anti-PD-1 / anti-PD-L1 antibodies and discovered that a pyridazinyl-thiazolcarboxamide compound has an inhibitory effect on DGKβ (DGKzeta), leading to the achievement of the present invention.The pyridazinyl-thiazolcarboxamide compound of the present invention has an inhibitory effect on DGK and can be used as a therapeutic agent for the treatment of cancer related to the activation of immune cells or cancer that offers resistance to treatment with anti-PD-1 antibodies / anti-PD-L1 antibodies.

The present invention relates to the technical field of electronic luminescent materials, and more particularly to a pyridazine-anthracene luminescent material and its application. The structure of the pyridazine-anthracene luminescent material is shown in the following general formula [I]: #imgabs0# General formula [I]; wherein R is a substituted or unsubstituted C1-C30 alkane chain, a C1-C30 aryl group, or a C1-C30 heteroaryl group, the substituent of the substituted or unsubstituted group is selected from hydrogen, deuterium, a C1-C30 alkane chain, a C1-C30 aryl group, or a C1-C30 heteroaryl group, and the heteroatom of the heteroaryl group is selected from any one or more of N, O, and S. The compound of the present invention has good molecular stability when used in organic electroluminescent devices. The prepared OLED device has excellent optoelectronic properties, high thermal stability, low driving voltage, and high luminous efficiency, which can extend the service life of the device and has good luminous performance, and can well meet the requirements of device manufacturers.

The invention belongs to the technical field of pyridazine derivative preparation. The invention provides a preparation method of a pyridazine derivative. The preparation method comprises the following steps: adding a compound with a general formula 1, iron nitrate nonahydrate, potassium carbonate and 4CzIPN into tetrahydrofuran for reaction; the reaction equation is shown in the specification; in the formula (I), R is hydrogen, 4-methyl, 4-methoxyl, 3-methoxyl, 2-iodine or 4-chlorine. The method provided by the invention is simple and convenient to operate and does not need high temperature and oxidant. The target product simultaneously contains diaza and pyridazine skeletons.