89 results about "Pyrazolopyridine" patented technology

The invention relates to a preparation method of 3-[(1S, 2S)-1-[5-[(4S)-2, 2-dimethyl oxacyclohexane-4-yl]-2-[(4S)-2-(4-fluoro-3, 5-dimethyl phenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6, 7-dihydro-4H-pyrazolo [4, 3-c] pyridine-5-carbonyl] indol-1-yl]-2-methylcyclopropyl]-4H-1, 2, 3-triazolo [4, 3-c] pyridine-5-carbonyl] indol-1-yl]-2-methylcyclopropyl]-1, 2, 4-triazolo [4, 3-c] pyridine-5- The invention relates to synthesis of 1, 2, 4-oxadiazole-5-one or a salt thereof, and related synthesis intermediate compounds.

Provided is a method of treating malignant tumor by an azabicyclic compound, particularly, with eye disorder reduced. The present invention provides a method for treating malignant tumor, comprising administering an effective amount of 3-ethyl-4-[3-(1-methylethyl)-4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-1H-pyrazolo[3,4-b]pyridin-1-yl]benzamide (compound 1) or a salt thereof to a patient in need thereof according to a dosing regimen, wherein the dosing regimen comprises administering the compound 1 or the salt thereof at a dose from 40 mg / body / day to 240 mg / body / day in terms of the amount of the compound 1 for consecutive days, and then providing a withdrawal period of at least 2 days.

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.

To provide pharmaceutical compositions which have the same action as GLP-1 peptide as a GLP-1 receptor agonist, are capable of noninvasive administration, and contain a compound having improved activity, metabolic stability, and bioavailability or a salt thereof or a solvate thereof, and to provide methods for preventing or treating non-insulin-dependent diabetes mellitus or obesity using the pharmaceutical compositions.SOLUTION: The present invention provides a pharmaceutical composition which contains as active ingredient a compound having a base skeleton represented by formula (I) in which an indole ring and a pyrazolopyridine skeleton are linked via a substituent, or a salt thereof or a solvate thereof, and is used in the prevention and treatment of non-insulin-dependent diabetes mellitus (type 2 diabetes mellitus) or obesity.SELECTED DRAWING: None

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 disclosure relates to compounds that act as inhibitors of the NLRP3 inflammasome, pharmaceutical compositions containing the compounds, and methods for treating inflammation and inflammation-aging-related disorders, including neurosensory disorders and other diseases associated with aging.

This invention discloses a class of pyrazolopyridine compounds linked by an aza-four-membered ring, or pharmaceutically acceptable salts thereof, and their applications. These compounds can serve as novel, highly selective PDE10A inhibitors for the treatment of peripheral tissue diseases, including: myocardial hypertrophy and cardiac dysfunction (heart failure), diabetes, hypertension, renal impairment and renal fibrosis, pulmonary inflammation and pulmonary fibrosis, immune dysregulation, and cancers (colon cancer, ovarian cancer, and lung cancer). Two strategies are employed to achieve high selectivity for PDE10A inhibition while simultaneously reducing the inhibitory effect on the central nervous system. First, molecular structure modification: structural optimization of the aza-four-membered ring-linked pyrazolopyridine compounds, such as increasing the ratio of N, O, and S atoms in the molecular structure to increase the polar surface area and reduce lipophilicity; and introducing hydrophilic groups to increase water solubility, thereby reducing the permeability of the compound to the blood-brain barrier (BBB). Second, targeted drug delivery to lung tissue via pharmaceutical formulation.

The invention belongs to the field of medicinal chemistry, and relates to pyrazolopyridyl oxyphenylurea derivatives, a pharmaceutical composition and application. The pyrazolopyridyl oxyphenylurea derivative with a brand-new parent nucleus structure is constructed on the basis of a biological electron isosteric principle. Performance test results show that the compound provided by the invention not only has an inhibition effect on an NEK7-NLRP3 pathway, but also shows remarkable anti-inflammatory activity; meanwhile, compared with a compound reported by the Halia Therpeutics company, the compound disclosed by the invention shows more excellent capability of inhibiting the release of inflammatory factors in an in-vitro experiment. Therefore, the novel compound provided by the invention has obvious advantages in the aspect of pharmacodynamics, and is expected to show better treatment effect and development potential in clinical application.

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 invention provides a synthesis method of apixaban. According to the synthesis method, a heterogeneous Pd monatomic catalyst is adopted to catalyze 1-(4-iodophenyl) piperidine-2-ketone and 1-(4-methoxyphenyl)-7-oxo-4, 5, 6, 7-tetrahydro-1H-pyrazolo [3, 4-c] pyridine-3-formamide to be subjected to a reaction, and apixaban is obtained. According to the method, the operation process is simple, the used Pd monatomic catalyst has high reaction selectivity on an N-H substrate, and the yield of apixaban is 94% or above. Compared with the traditional method, the synthesis method provided by the invention can select water as a solvent, can react under normal pressure, directly utilizes the Pd monatomic catalyst to synthesize the target product in one step, is faster and more efficient, and is environment-friendly and mild.

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).

The present invention relates to a substituted thienyl-5-fluoro-1H-pyrazolopyridine compound and a use thereof. The present invention specifically relates to a compound as shown in a formula (I), a preparation method for the compound, a pharmaceutical composition and a combination product containing the compound, and a use of the compound, the pharmaceutical composition or the combination product in preparation of drugs for treating and / or preventing diseases such as heart failure.

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.

Provided is a novel compound serving as an analogue to be removed from API or a preparation. Further provided is a reference standard of an analogue for use in the quality control of a medicament. Analogue 1: 3-ethyl-4-{4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3,3′-di(propan-2-yl)-1′H-[1,4′-bipyrazolo[3,4-b]pyridin]-1′-yl}benzamide. Analogue 2: 3-ethyl-4-fluorobenzamide. Analogue 3: N-[1-(4-carbamoyl-2-ethylphenyl)-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-3-ethyl-4-{4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzamide. Analogue 4: 3-ethyl-4-{14-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-13,23,33-tri(propan-2-yl)-31H-[11,24:21,34-terpyrazolo[3,4-b]pyridin]-31-yl}benzamide. Analogue 5: 4,4′-(1H,1′H-[4,4′-biimidazole]-1,1′-diylbis{[3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridine-4,1-diyl]})bis(3-ethylbenzamide). Analogue 6: 4-{4,6-bis[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl }-3-ethylbenzonitrile. Analogue 7: 4-{4,6-bis[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl }-3-ethylbenzamide. Analogue 8: 4-[4-ethoxy-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl]-3-ethylbenzamide. Analogue 9: 3-ethyl-4-[4-methoxy-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl]benzamide.

Provided is a pharmaceutical composition containing compound 1 and having excellent disintegrability and bioavailability.　This pharmaceutical composition contains crystalline cellulose and a granulated substance containing 3-ethyl-4-{4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridine-1-yl}benzamide or a pharmaceutically acceptable salt thereof, and has a disintegration time of 360 seconds or less in a coated tablet state.

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.

To provide: a compound as a GLP-1 receptor agonist which has the same effect as GLP-1 peptide, may be non-invasively administered and is improved in activity, metabolic stability and bioavailability; and a preventive or therapeutic agent for non-insulin-dependent diabetes mellitus (type 2 diabetes) or obesity containing the compound as an active ingredient.SOLUTION: The present invention provides: a compound represented by Formula (I) in the figure, in which an indole ring or pyrrolo[2,3-b]pyridine ring and a pyrazolopyridine skeleton are bound to each other through a substituent; or a salt thereof; or a solvate of them.SELECTED DRAWING: None

The application discloses a pyrazolopyridine calnexin ligand and a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The structure of the pyrazolopyridine calnexin ligand is shown in the following formula: wherein R1 is preferably or R2 is preferably. Experiments prove that the pyrazolopyridine derivative disclosed by the application has a proliferation inhibiting effect on various tumor cells, and has a stronger IC 50 on pancreatic cancer cells; has a significant inhibiting effect on the adipogenic differentiation of fat cells 3T3-L1, has good weight loss and blood lipid reducing activities, and has good long-term drug safety.