363 results about "Indazole" patented technology

Disclosed herein are compounds and methods of treating diseases and / or conditions associated with FGFR inhibition.

The present invention relates to compounds of formula (I) possessing an indole moiety linked to an indazole moiety, to compounds having similar core structures, and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present invention further relates to methods of synthesising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by Factor B inhibition.

The invention belongs to the technical field of pyrimidine [1, 2-b] indazole derivative synthesis, and particularly relates to a fluoro pyrimidine [1, 2-b] indazole compound and a preparation method thereof. The preparation method specifically comprises the following steps: by taking an enamine compound as shown in a formula 1, heteroarylamine as shown in a formula 2 and polyfluoroalkyl halide as shown in a formula 3 as reaction substrates, mixing the reaction substrates, a catalyst and a solvent, and carrying out cyclization reaction in a protective gas atmosphere and under blue light irradiation to obtain the fluoropyrimidine [1, 2-b] indazole compound. The fluorine atom substituted or multi-fluoroalkyl substituted pyrimidine [1, 2-b] indazole derivative can be selectively constructed in the same reaction system, the diversity of the structure is obviously expanded, and the reaction conditions are mild and green and environment-friendly.

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 combination of (S)-2-(5-((3-ethoxypyridin-2-yl)oxy)pyridin-3-yl)-N-(tetrahydrofuran-3-yl)pyrimidine-5-carboxamide or pharmaceutically acceptable salt thereof, and 4-(4-(1-Isopropyl-7-oxo-1,4,6,7-tetrahydrospiro[indazole-5,4′-piperidine]-1′-carbonyl)-6-methoxypyridin-2-yl)benzoic acid or pharmaceutically acceptable salt thereof, for treatment of diseases, including non-alcoholic steatohepatitis (NASH), in mammals are described herein.

The present disclosure relates to methods and compositions for treating cancer with a macrocyclic indazole compound in combination with at least one other cancer therapeutic, such as a Bcl-2 inhibitor, a FLT3 inhibitor, a KRAS inhibitor, an ALK inhibitor, a PARP inhibitor, an EGFR inhibitor, a chemotherapy, and the like.

The present disclosure relates generally to inhibitors of KIF18A, compositions thereof, and methods of using said compounds and compositions thereof. More specifically, the present disclosure relates to indole and indazole inhibitors of KIF18A and methods of their use for treating disease mediated by KIF18A, such as cancer.

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The invention belongs to the field of analytical chemistry, relates to material preparation, and particularly discloses a preparation method of a copper-doped covalent organic framework and application of the copper-doped covalent organic framework in adrenaline colorimetric detection. Firstly, 1H-indazole-4, 7-diamine (Iz) and 1, 3, 5-triformyl phloroglucinol (Tp) are used as monomers to synthesize a novel covalent organic framework (Iz-Tp COF) through a Schiff base reaction, copper ions are introduced into the Iz-Tp COF framework to prepare a novel metal covalent organic framework (Iz-Tp (at) Cu), and then according to the phenomenon that the Iz-Tp (at) Cu can catalyze oxidation color development of epinephrine, the metal covalent organic framework (Iz-Tp (at) Cu can catalyze oxidation color development of epinephrine. According to the present invention, the simple, sensitive and efficient adrenaline colorimetric detection method is established, the test conditions are finally optimized, the standard addition method is combined to accurately determine the adrenaline concentration in the urine, and the good practical application value is provided.

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 invention discloses an HPK1 small-molecule inhibitor based on a novel indazole skeleton and application of the HPK1 small-molecule inhibitor, and belongs to the technical field of medical chemistry. The HPK1 small-molecule inhibitor is a compound as shown in a formula (I) or an enantiomer thereof, a mixture of the enantiomer, a mixture of two or more diastereoisomers, a tautomer, a mixture of two or more tautomers, or an isotope variant or a pharmaceutically acceptable salt, a solvate, a hydrate or a prodrug thereof. The novel HPK1 small-molecule inhibitor skeleton disclosed by the invention shows a very strong inhibition effect on HPK1 and has a relatively good application prospect.

The invention relates to application of an amide ligand and a copper catalyst in preparation of an amino indazole piperidine compound. The indazole piperidine compound is prepared by reacting a halogen-substituted indazole piperidine compound with an ammonia reagent, the reaction is carried out under the action of an amide ligand and a catalyst, the amide ligand is # imgabs0, the structural formula of the amide ligand is # imgabs1 # or L-hydroxyproline, and the catalyst is a cuprous compound.

The invention provides a zinc-based metal organic framework material as well as a preparation method and application thereof. The zinc-based metal organic framework material comprises a mixed coordination framework which is formed by coordination of N and O and has pcu topology, and the minimum asymmetric unit of the zinc-based metal organic framework material is composed of three zinc ions, three deprotonated 1H-indazole-5-carboxylic acids and bridging water molecules. The preparation method comprises the following steps: heating a zinc salt aqueous solution to a reaction temperature, keeping for 30-40 minutes, cooling, and filtering for later use; dissolving an organic ligand in an organic solvent to obtain a ligand solution, heating to a reaction temperature, keeping for 30-40 minutes, and filtering for later use; mixing the standby solutions obtained by respective filtration, removing impurities, and adding a regulator to obtain a mixed solution; and carrying out standing reaction and purification treatment. The zinc-based metal organic framework material provided by the invention is a porous material formed by coordination self-assembly of an organic ligand and zinc ions, has a large specific surface area and aromatic ring modified pore walls, is more beneficial to adsorption of propylene and propane and weakening of adsorption of other low-carbon hydrocarbons, and is high in separation selectivity.

Provided herein are compounds of Formula (I):or a pharmaceutically acceptable salt thereof. The provided compounds are useful Poly ADP-ribose glycohydrolase (PARG) inhibitors. Additional utilities and advantages are described herein.

Indazolo-amino-pyrimidinone compounds of formula I; (I), for use in methods of inhibiting both Wee1 A kinase and Myt1 kinase.

The present invention provides compounds indicated by general formula [1] and having mPGES-1 inhibitory activity, a pharmaceutically acceptable salt thereof, or a solvate thereof (in the formula, R1 and R2 each independently indicate hydrogen, halogen or substitutable alkyl, R3 indicates —SO2 R5 or —COR5, R4 indicates substitutable alkyl, cycloalkyl, aryl, heteroaryl, saturated heterocyclic group or arylalkyl, and R5 indicates a substitutable alkyl, cycloalkyl, aryl, heteroaryl, saturated heterocyclic group, alkynyl or arylalkyl).

Novel compounds of Formula (I), and the pharmaceutically acceptable salts thereof, are inhibitors of NLRP3 and may be useful in the treatment, prevention, management, amelioration, control, and suppression of diseases mediated by NLPR3. The compounds of the present invention may be useful in the treatment, prevention or management of diseases, disorders and conditions mediated by NLRP3 such as, but not limited to, obesity, gout, pseudogout, CAPS, NASH, MASH, fibrosis, osteoarthritis, atherosclerosis, heart failure, idiopathic pericarditis, myocarditis, atopic dermatitis, hidradenitis suppurativa, inflammatory bowel disease, cancer, Alzheimer's Disease, Parkinson's Disease, dementia with Lewy bodies (DLB), and traumatic brain injury.

The invention provides compounds that degrade the epidermal growth factor receptor (EGFR) including mutant forms via the ubiquitination of the EGFR protein and subsequent proteasomal degradation. The compounds are useful for the treatment of various cancers.

Disclosed are processes for the preparation of the pesticide N-(1-methylcyclopropyl)-2-(3-pyridinyl)-2H-indazole 4-carboxamide. Also disclosed are methods for the preparation of intermediates of thereof N-(1-methylcyclopropyl)-2-(3-pyridinyl)-2H-indazole 4-carboxamide.

The invention provides a compound as shown in a formula (I) and a racemate, a stereoisomer, a tautomer, an isotope label, nitrogen oxide, a solvate, a polymorphic substance, a metabolite, ester, a prodrug or pharmaceutically acceptable salt thereof. The compound has a good FGFR2 / 3 inhibition effect, can be used for treating or preventing FGFR2 / 3 mediated diseases and diseases, and can be used for preparing medicines for treating or preventing the diseases and diseases. # imgabs0 #

The present invention relates to an oral capsule composition comprising 3-[(1S, 2S)-1-[5-[(4S)-2, 2-dimethyloxane-4-yl]-2-[(4S)-2-(4-fluoro-3, 5-dimethylphenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6, 7-dihydro-4H-pyrazolo [4, 5-a] pyrimidine-2-yl]-3-(4-fluoro-1-methylindazol-5-yl)-4-methyl-6, 7-dihydro-4H-pyrazolo [4, 5-a] pyrimidine-2-yl]-3-(4-fluoro-1-methylindazol-5-yl)-4, 4 '- The invention relates to a pharmaceutical composition, in particular to a pharmaceutical composition containing 4-(2, 3-c) pyridine-5-carbonyl] indole-1-yl]-2-methylcyclopropyl]-4H-1, 2, 4-oxadiazole-5-ketone or a pharmaceutically acceptable salt thereof. And a pH adjusting agent.

The present invention relates to a novel polymorph of (1R,2R,3aS,3bR,10aS,10bR,11S,12aS)-5,10b-difluoro-1-(((fluoromethyl)thio)carbonyl)-11-hydroxyl-2,10a,12a-trimethyl-7-phenyl-1,2,3,3a,3b,7,10,10a,10b,11,12,12a-dodecylhydrocyclapenta[5,6]napththo[1,2-F]indazole-1-furan-2-carboxylate ester as shown in formula (I), a preparation method therefor, and a use thereof. The crystal form of the present invention has characteristics such as a significant pharmaceutical effect, good stability, high yield, and high purity, and is beneficial for the selection and design of a drug administration route and the determination of a drug preparation process parameter, thereby improving drug production quality.

The present invention relates to an indazole derivative or a pharmaceutically acceptable salt thereof, and a composition for preventing, treating, or ameliorating cancer, comprising, as an active ingredient, the derivative or a pharmaceutically acceptable salt thereof. The indazole derivative of the present invention is designed to provide strong binding to the C-terminal domain of Hsp90, and does not affect the composite structure of Hsp90 and HSF-1, thus not inducing the activation of HSF-1 or the expression of Hsp genes, thereby effectively promoting apoptosis of cancer cells. Thus, the indazole derivative of the present invention can be used in the prevention, treatment, or amelioration of cancer.

The present invention relates to the preparation of compositions comprising sodium trans-[tetrachlorobis(1H-indazole)ruthenate (III)]. Synthesis and formulation preparation is detailed. Impurity profiles are also discussed. Compositions herein are useful for anti-cancer applications.

An indazole derivative, a preparation method therefor, and a pharmaceutical application thereof. In particular, the present invention relates to an indazole derivative represented by general formula (I), a preparation method therefor, a pharmaceutical composition comprising the derivative, and a use of the derivative as an estrogen receptor modulator in the prevention and / or treatment of an estrogen receptor mediated or dependent disease or condition, the disease being particularly preferably breast cancer. The definition of each substituent in the general formula (I) is the same as that in the description.

The present application provides a kind of compound with indazole group, THR beta receptor agonist and use, compound with indazole group or its pharmaceutically acceptable salt.The present application develops a kind of THR beta selective agonist with better specificity and drugability, the present agonist is better selective agonist THR beta and avoids the activation of THR alpha, separates the harmful influence of thyroid hormone excess from potential beneficial effects such as lowering cholesterol and blood lipids, provides a kind of new type of treatment drug with broad prospects for treating a series of major metabolic diseases in urgent need of solution.

The present application relates to novel substituted indazoles, to processes for preparation thereof, to the use thereof alone or in combinations for treatment and / or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and / or prophylaxis of diseases, especially for treatment and / or prophylaxis of endometriosis and endometriosis-associated pain and other endometriosis-associated symptoms such as dysmenorrhoea, dyspareunia, dysuria and dyschezia, of lymphoma, rheumatoid arthritis, spondyloarthritis (especially psoriatic spondyloarthritis and Bekhterev's disease), lupus erythematosus, multiple sclerosis, macular degeneration, COPD, gout, fatty liver disorders, insulin resistance, neoplastic disorders and psoriasis.

The invention provides a method for preparing a chiral helicene compound through cyclization reaction of an iridium-catalyzed 3-aryl indazole biaryl compound and disubstituted alkyne. The method comprises the following steps: under the action of an iridium catalyst, a chiral cyano phosphorus-oxygen ligand and an additive, carrying out an intermolecular asymmetric carbon-hydrogen bond activation reaction on a 3-aryl indazole biaryl compound and disubstituted alkyne, and after the reaction is finished, separating to obtain the chiral diazaspirene-containing compound, according to the invention, synthesis of the chiral helicene compound is realized through a transition metal catalysis asymmetric carbon-hydrogen bond activation method, the research technology of Cp metal catalysis asymmetric carbon-hydrogen bond activation is further developed, and the synthesis strategy of the chiral helicene compound is expanded at the same time; reaction substrates are wide in universality, and chiral control in the reaction process is realized through the chiral cyano phosphine oxide, so that the product has very high enantioselectivity; various chiral helicene compounds are synthesized, the synthesis method is simple and convenient, and the atom economy is high.