133 results about "Pyrazolopyridine" patented technology

Disclosed is a series of pyrazolopyridine compounds, and application thereof in the preparation of RET kinase inhibitors for treatment. Specifically disclosed is the compound represented by formula (I), or a pharmaceutically acceptable salt thereof.

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.

The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.

The present invention provides a pharmaceutical composition containing Compound 1, which has excellent disintegrability and bioavailability. The present invention relates to a pharmaceutical composition comprising: a granulated material 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] pyridin-1-yl} benzamide or a pharmaceutically acceptable salt thereof, and a crystalline cellulose, the granulated material being characterized in that: the granulated material contains a compound represented by general formula (1); the pharmaceutical composition has a disintegration time within 360 seconds in a coated tablet state.

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.

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

The invention discloses an aza-four-membered ring connected pyrazolopyridine compound or pharmaceutically acceptable salt and application thereof, and the compound with the structure can be used as a novel high-selectivity PDE10A inhibitor for treating peripheral tissue diseases such as cardiac hypertrophy and cardiac dysfunction (heart failure), diabetes, hypertension, renal function impairment and renal fibrosis. Lung inflammation and pulmonary fibrosis, immune regulation disorder and cancers (colon cancer, ovarian cancer and lung cancer). Through strategies in two aspects, the inhibition effect of the compound on a PDE10A high-selectivity inhibitor is reduced while the inhibition effect of the compound on a central nervous system is reduced. Firstly, in the aspect of molecular structure modification, the structure of the pyrazolopyridine compound connected with the aza-four-membered ring is optimized, for example, the polar surface area of molecules is increased by increasing the proportion of the number of N, O and S atoms in the molecular structure, and the fat solubility is reduced; and hydrophilic groups are introduced to increase water solubility and the like, so that the permeability of the compound to the blood brain barrier BBB is reduced. And 2, targeted drug delivery of lung tissues is realized by means of a pharmaceutical preparation.

The invention belongs to the technical field of fuel cells, and discloses a metal organic framework material with proton conductivity and a preparation method and application thereof. Pyrazolo [3, 4-c] pyridine is used as a ligand, a binuclear cuprous cluster is used as a connection point, a two-dimensional layered structure is constructed through the ligand and the binuclear cuprous cluster, a cuprous multi-nitrogen heterocyclic metal organic framework is formed, the cuprous multi-nitrogen heterocyclic metal organic framework is oxidized, and the cuprous multi-nitrogen heterocyclic metal organic framework is obtained. Divalent copper ions and monovalent copper ions exist in the oxidized cuprous multi-nitrogen heterocyclic metal organic framework, and the metal organic framework material with proton conductivity is obtained. The proton conductivity of the metal organic framework material can be remarkably improved by adopting a metal post-synthesis modification oxidation technology, and the proton conductivity of the metal organic framework material is comparable with that of commercial Nafion, and an oxidized sample shows extremely high chemical stability; the problem of poor stability of a non-fluorinated hydrocarbon polymer proton exchange membrane and inorganic solid acid researched in the prior art is solved.

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.

The invention discloses a phenyl-substituted pyrazolopyridine compound as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The structure of the compound is as follows: # imgabs 0 #, wherein R1 is any one of the following structures: # imgabs 1 #; and R2 is any one of the following structures: # imgabs2. The compound has the beneficial effects that the compound has a proliferation inhibition effect on various tumor cells and can selectively inhibit proliferation of triple negative breast cancer cells MDA-MB-468, the half inhibitory concentration IC50 of the compound 8 is 2.500 M, the selection index SI is 8.428, and the compound 8 can be deeply developed as a lead compound for resisting triple negative breast cancer.

The present invention discloses a novel pyrazolo[1,5-a]pyridine derivative, a preparation method thereof and medical application thereof. More specifically, the pyrazolo[1,5-a]pyridine derivative of the present invention can be used as a drug for treating proliferative diseases and other diseases related to abnormal expression of TRK or various kinases such as RET, FGHR, PDGFR, and VEGFR. Its structure is shown in the general formula (I), wherein L 1 , L 2 , L 3 , R 1 , R 2 and R 3 Definitions see the manual:

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 invention discloses a preparation method of 6-ethynyl pyrazolo [1, 5-a] pyridine, which comprises the following steps: carrying out a sonogashira coupling reaction on 2, 5-dibromopyridine to obtain 2, 5-bis ((trimethylsilyl) ethynyl) pyridine; carrying out nitrogen amination reaction by using a nitrogen aminating agent, so as to obtain 1-amino-2, 5-bis ((trimethylsilyl) ethynyl) pyridine; and carrying out ring closing under the action of a catalyst, and carrying out a desilicication methyl reaction by using tetrabutylammonium fluoride to obtain the 6-ethynyl pyrazolo [1, 5-a] pyridine. According to the preparation method of the 6-ethynyl pyrazolo [1, 5-a] pyridine, low-cost raw materials are used, reaction conditions are easy to control, the reaction selectivity is high, byproducts are few, and the preparation method is suitable for large-scale production of the 6-ethynyl pyrazolo [1, 5-a] pyridine.

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 provides a novel compound which is an analogue to be removed from an API or a preparation, and also provides a standard substance for an analogue to be used in the management of the quality of a pharmaceutical product. The analogue 1: 3-ethyl-4-{4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3, 3 '-di (propane-2-yl)-1' H-[1, 4 '-bipyrazolo [3, 4-b] pyridine]-1'-yl} benzamide analogue 2: 3-ethyl-4-fluorobenzamide analogue 3: N-[1-(4-carbamoyl-2-ethylphenyl)-3-(propane-2-yl)-1H-pyrazolo [3, 4-b] pyridine]-1 '-fluorobenzamide analogue 1: 3, and the analogue 2: 3: 4. 4: 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 analogues 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-1-yl]-3: 3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo [3, 4-b] benzamide analogues. The preparation method comprises the following steps: preparing 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] pyridine]-31-yl} benzamide analogue; the 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] pyridine-1-yl}-3-ethylbenzonitrile analogue has a structural formula shown in the description. The present invention relates to a compound represented by the following formula (I): 4-[4-ethoxy-3-(propane-2-yl)-1H-pyrazolo [3, 4-b] pyridine-1-yl]-3-ethylbenzamide analogue 8: 4-[4-ethoxy-3-(propane-2-yl)-1H-pyrazolo [3, 4-b] pyridine-1-yl]-3-ethylbenzamide analogue 9: 3-ethyl-4-[4-methoxy-3-(propane-2-yl)-1H-pyrazolo [3, 4-b] pyridine-1-yl] benzamide.

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.

The present disclosure relates to compounds that act as inhibitors of NLRP3 inflammasomes; pharmaceutical compositions comprising such compounds; and methods of treating conditions associated with inflammation and inflammatory senescence, including sensory neurological diseases and other diseases associated with senescence.