57 results about "Pyrazolopyridine" patented technology

The invention provides a preparation method of a pyrazolopyridine derivative (formula (I)). The method has the advantages of mild reaction conditions, simple operation, high reaction yield, high product purity and convenient post-treatment, and is suitable for industrial production.

The invention relates to a synthesis method of an intermediate for preparing a THR-beta agonist, and belongs to the technical field of medicine synthesis. The synthesis method of the intermediate for preparing the THR-beta agonist is realized by utilizing a substitution reaction of 1H-pyrazolo [4, 3-b] pyridine and 2, 6-dichloro-p-nitrofluorobenzene and a Katada reaction, has the advantages of easiness in large-scale production, controllable quality, controllable cost and the like, and compared with an existing preparation method, the yield of the preparation method disclosed by the invention is greatly improved, and the synthesis method is suitable for industrial production. The raw materials are cheap, easy to obtain, simple and efficient, and have great industrialization prospects.

The invention belongs to the field of Velciguat synthesis, and particularly relates to a preparation method of Velciguat and an intermediate product thereof. The preparation method of the Velciguat comprises the following steps: (1) reacting aminomalononitrile with methyl chloroformate to generate an intermediate product I; (2) carrying out ring closing on the intermediate product I and formamidine under an alkaline condition to obtain an intermediate product II; (3) carrying out bromination reaction on the intermediate product II and N-bromosuccinimide to obtain an intermediate product III; (4) reacting the intermediate product III with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate product IV; and (5) carrying out a reaction on the intermediate product IV and 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo [3, 4-b] pyridine to prepare the viriciguat. The method is simple to operate, low in cost and safe in production. The invention also provides the intermediate product obtained by the preparation method.

New derivatives of 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl) phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo [3,4c] pyridine-3-carboxamide (Apixaban) able to increase its water solubility. These derivatives are cocrystals derivatives ofApixaban of different acids, from which the most outstanding are the following: Apixaban Malonic Acid derivative, Apixaban-a-Ketoglutaric Acid derivative, Apixaban-Gallic Acid derivative, Apixaban-Maleic Acid derivative, Apixaban-L-Tartaric Acid derivative, and Apixaban Citric Acid derivative.

The present invention is related to pyrazolo pyridine derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and / or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

The present application relates to a compound of formula (I) or formula (II), wherein L, R1, R2, R3 and R4 are as defined in the claims. The compounds of formula (I) or formula (II) are useful as medicaments for modulating SIK activity in autoimmune disorders, inflammation and other disorders. (I) and (II).

To address the shortcomings of existing antitumor chemotherapy drugs, this invention provides a class of pyrazolopyridone derivatives and their preparation method. The compounds are structurally designed and modified using pyrazolopyridone as the parent core, resulting in a class of pyrazolopyridone derivatives (I) with good stability and significant antitumor effects: wherein: R 1 The compound is 4-methoxyphenyl,N-phenylbenzamide. This invention relates to the field of tumor treatment, specifically to a class of novel pyrazolopyridone derivatives with advantages such as structural stability and ease of preparation. These compounds can be used to treat diseases such as tumors and condyloma acuminata.

To provide a new compound useful for treatment, prevention and / or diagnosis of seizure or the like in diseases accompanied by epileptic seizure or convulsive seizure (including multidrug-resistant seizure, intractable seizure, acute symptomatic seizure, febrile seizure and status epilepticus).SOLUTION: There are provided a compound represented by formula [I] and a salt thereof. Ring C is selected from pyridazine, pyrimidine, indole, pyrrolopyridine, indazole, pyrazolopyridine, imidazopyridine, imidazopyrazine, imidazopyridazine, triazolopyridine, pyrazolopyrimidine, imidazopyrimidine, triazolopyrimidine, isoquinoline, naphthyridine, quinazoline, quinoxaline, benzodioxole, oxazine, oxazepine, benzothiazole, and triazolopyridazine, with the proviso that pyrimidine-2, 4-dione and dihydropyrimidine-2, 4-dione are excluded.SELECTED DRAWING: None

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a 6,5-heterocyclic structure (e.g., compounds having a imidazopyridine, imidazopyrimidine, imidazopyrazine, imidazopyridazine, imidazotriazine, benzoimidazole, benzotriazole, benzoisoxazole, purine, indazole, triazolotriazine, triazolopyridazine, triazolopyrimidine, triazolopyrazine, triazolotetrazine, triazolopyridine, pyrazolopyrazine, pyrazolopyrimidine, pyrazolopyridazine, pyrazolotriazine, pyrazolopyridine, isoxazolopyrazine, isoxazolopyrimidine, isoxazolopyrdiazine, isoxazolotriazine, or isoxalopyridine structure) which function as inhibitors of DYRK1A, DYRK1B, and Clk-1, and their use as therapeutics for the treatment of Alzheimer's disease, Down syndrome, diabetes, glioblastoma, autoimmune diseases, cancer (e.g., glioblastoma, prostate cancer), inflammatory disorders (e.g., airway inflammation), and other diseases.

The application provides a synthesis method of apixaban. The synthesis method adopts a heterogeneous Pd monatomic catalyst to catalyze the reaction of 1-(4-iodophenyl)piperidin-2-one and 1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide to obtain apixaban. The method is simple in operation process, the Pd monatomic catalyst has high reaction selectivity to N-H substrates, and the yield of apixaban is more than 94%. Compared with the traditional method, the synthesis method provided by the application can select water as a solvent, can also react under normal pressure, directly utilizes a Pd monatomic catalyst to synthesize a target product in one step, is more fast and efficient, and is environment-friendly and mild.

The present invention relates to a pyrazolo[1,5-a]pyridine derivative, a preparation method therefor, and a composition and a use thereof. Specifically, the present invention relates to the compound of formula (I) and the use thereof for the treatment and / or prevention of wild type, gene-fusion type (including but not limited to KIF5B, CCDC6 and NCOA4) and mutant type (including but not limited to V804, G810 and M918) RET kinases-related diseases, including diseases or conditions mediated by RET kinase.

The present invention provides a novel 5-fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo [3, 4-b]pyridine-3-carboximidamide formate compound of formula (IV) and process for preparation thereof. The present invention further provides for the use of compound of formula (IV) for the preparation of vericiguat compound of formula I. The present invention also relates to process for the preparation of vericiguat Modification form II, vericiguat Modification form III, vericiguat monohydrate and dihydrate.

The application belongs to the field of vixepiromide synthesis, and particularly relates to a preparation method of vixepiromide and intermediate products thereof. The preparation method of vixepiromide comprises the following steps: (1) reacting aminopropandinitrile with methyl chloroformate to generate an intermediate product one; (2) ring closing the intermediate product one with formamidine under alkaline conditions to generate an intermediate product two; (3) performing bromination on the intermediate product two with N-bromosuccinimide to generate an intermediate product three; (4) reacting the intermediate product three with pinacol diboron under the action of a catalyst to generate an intermediate product four; and (5) reacting the intermediate product four with 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridine to generate vixepiromide. The application has the advantages of simple operation, low cost and safe production. The application further provides the intermediate products generated in the above preparation method.

The present disclosure relates to methods of treatment of asthma, COPD, Asthma-COPD Overlap Syndrome (ACOS), and chronic bronchitis, or a combination thereof, with formulations comprising (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridin-3-yl)-1,2-dihydro-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)-3-oxopropanenitrile.

This invention discloses substituted pyrazolopyridine as a GluN2B receptor ligand. Such compounds can be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by GluN2B receptor activity, including those involving GluN2B receptor modulation and neutralization.

The present invention relates to the compound shown in general formula (I) or to a stereoisomer, tautomer, deuterated substance, solvate, prodrug, metabolite, pharmaceutically acceptable salt or eutectic crystal thereof, and to an intermediate and a preparation method thereof, and also to an application thereof in the preparation of a medicine for treating diseases related to USP1 activity or expression.

The present disclosure relates to methods of treatment of asthma, COPD, Asthma-COPD Overlap Syndrome (ACOS), and chronic bronchitis, or a combination thereof, with formulations comprising (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridin-3-yl)-1,2-dihydro-3H-imidazo[4,5-b]pyridin-3-yl)piperidin-1-yl)-3-oxopropanenitrile.

Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopologues, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and / or preventing diseases (e.g., proliferative diseases (e.g., cancers and benign neoplasms), inflammatory diseases (e.g., rheumatoid arthritis), and vascular diseases (e.g., atherosclerosis) in a subject. Provided are methods of inhibiting a INK (e.g., JNK1, JNK2, or JNK3) in a subject.

The present application relates to 5-[1,2,4-oxadiazole]-6-oxygen-pyrazolopyridine derivatives and preparation method and application thereof, and the 5-[1,2,4-oxadiazole]-6-oxygen-pyrazolopyridine derivatives and pharmaceutically acceptable salts thereof, the general formula is as shown in formula (II): wherein, the definition of substituent group is described in the specification. The 5-[1,2,4-oxadiazole]-6-oxygen-pyrazolopyridine derivatives and pharmaceutically acceptable salts thereof of the present application have the functions of inhibiting Hsp110-STAT3 interaction, thereby down-regulating p-STAT3 and c-Myc levels, inhibiting pulmonary arterial endothelial cell proliferation, migration and apoptosis resistance, reducing pulmonary arterial pressure and improving the degree of pulmonary vascular remodeling, and further playing the role of anti-pulmonary arterial hypertension.

The invention discloses the crystal form, preparation method and application of an alkynyl compound, its salt and solvent compound. The invention specifically discloses 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-yl)methyl)-3-(trifluoromethyl)phenyl) benzamide crystal form I and 3-((1H-pyrazolo [3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-yl)methyl)-3-(trifluoromethyl)phenyl) benzamide fumarate crystal form II. The crystal form of the invention has good stability and has important value for drug optimization and development.

Provided is a method for preparing a kinase inhibitor. Specifically, disclosed is a method for preparing a compound, i.e. 6-(3-hydroxy-3-methylazetidin-1-yl)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile. Further disclosed are an intermediate for preparing such inhibitor and a method for synthesizing a required intermediate. The preparation method involves a low reaction temperature and simple process steps, has a very high yield and product purity, and is suitable for industrial production.

The invention discloses a novel synthesis method of 5-aryl-3-alkyl pyrazolo [1, 5-a] pyridine, which comprises the following specific synthesis steps: adding an X2 donor compound into a solvent containing a compound SM at 0-5 DEG C, stirring at 0-5 DEG C for complete reaction, and performing post-treatment to obtain a compound 1; adding the compound 1 into a solvent, adding an organic metal reagent at 0-5 DEG C in a protective atmosphere, stirring at room temperature for complete reaction, and performing post-treatment to obtain a compound 2; dissolving the compound 2 and triethyl silane in a solvent, adding trifluoroacetic acid, stirring to react completely, and performing post-treatment to obtain a compound 3; under a protective atmosphere, dissolving the compound 3, Pd (dppf) Cl2, B2Pin2 and alkali in an organic solvent, and carrying out reflux stirring reaction completely to obtain a compound 4; and under a protective atmosphere, adding water, Pd (dppf) Cl2 and ArX into the reaction liquid containing the compound 4, carrying out reflux stirring to completely react, and carrying out post-treatment on the reaction liquid to obtain a target compound 5. The method is short in step, easy to operate in each step, high in yield and suitable for large-scale amplification.

The present application relates to pyrazolopyridine compounds, and pharmaceutical compositions, preparation methods and uses thereof, in particular, the present application relates to a compound shown in formula I or its pharmaceutically acceptable form, and pharmaceutical compositions, preparation methods and uses thereof. The compound can be used as a drug for treating cancer or fibrosis disease,

The present disclosure provides compounds of the formula: for use in the treatment of systemic sclerosis, fibrosis (e.g. pulmonary fibrosis), achondroplasia, thanatophoric dysplasia (e.g. type I), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), muenke syndrome or cancer.

The present disclosure relates to the use of neuroactive steroids, including alfaxalone, alfadolone, alfadolone acetate, pregnanediol, pregnanolone, ent-pregnanolone, pregnanedione, allopregnanediol, allopregnanedione, acebrochol, ganaxolone, hydroxydione, minaxolone, renanolone, (2β,3α,5β)-21-chloro-3-hydroxy-2-morpholin-4-ylpregnan-20-one (Org-20599), 2β-(2,2-dimethyl-4-morpholinyl)-3α-hydroxy-11,20-dioxo-5α-pregnan-21-yl methanesulfonate (Org-21465), 20-(hydroxyimino)pregn-4-en-3-one (EIDD-036), posovolone (Co 134444), zuranolone (SAGE-217), 3α-hydroxy-3β- methyl-21-(pyrazolo[3',4'-c]pyridin-2'-yl)-19-nor-5β-pregnan-20-one (SGE-872), alfaxalone / alfadolone (CT1341), (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β- OH), (3α,5α)-3-hydroxy-13,24-cyclo-18,21-dinorchol-22-en-24-ol (CDNC24), 3α- dihydroprogesterone (3α-DHP), ent-progesterone, dihydrodeoxycorticosterone (DHDOC), tetrahydrodeoxycorticosterone (THDOC), and betaxalone, for treating or at least partially inhibiting the development or progression of an infection caused by a neurotropic virus in a subject. This disclosure also relates to the use of neuroactive steroids for treating or at least partially inhibiting the development or progression of a condition associated with an infection caused by a neurotropic virus, such as encephalopathy or acute encephalitis.

To provide a compound for treating or preventing a disease in which GLP-1 receptor plays a role.SOLUTION: The application relates to a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, as well as a pharmaceutical composition comprising the compound of Formula (I).SELECTED DRAWING: None