12 results about "Azacyclobutane" patented technology

This article describes pharmaceutical formulations of the farnesol X receptor agonist 3-hydroxyazacyclobutane-trans-1-carboxylic acid 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl)bicyclo[2.2.2]octane-1-yl)methyl)carbamoyl)cyclohexyl ester, and methods of using such pharmaceutical formulations to treat conditions, diseases, or symptoms associated with farnesol X receptor activity.

Provided herein are solid forms, e.g., polymorphs, of 2-(3-((7R,8aS)-7-fluorohexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-1-(5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)azetidin-3-yl)acetonitrile, which are useful for treating kinase-related diseases or disorders. The solid forms, and compositions thereof, are useful for treating diseases in a subject, including, but not limited to, ocular diseases such as glaucoma, ocular hypertension, ocular wound repair, neurodegenerative ocular diseases, retinal detachment, and non-ocular diseases such as nerve injury, or skin wound repair, or inflammatory diseases, among others. (Compound 1) TIFF2026501674000028.tif4839

The invention relates to a stable imidazo [1, 2-a] pyridine derivative pharmaceutical composition and application thereof.The pharmaceutical composition comprises an active pharmaceutical ingredient and auxiliary materials, the active pharmaceutical ingredient is (azetidine-1-yl) (8-(2, 6-dimethyl benzylamino)-2, 3-dimethyl imidazo [1, 2-a] pyridine-6-yl) ketone or salt thereof, and the auxiliary materials are selected from the group consisting of 2-(2, 6-dimethyl benzylamino)-2, 3-dimethyl imidazo [1, 2-a] pyridine-6-yl)-2, 3-dimethyl imidazo [1, 2-a] pyridine-6-yl) ketone or salt thereof. The auxiliary material comprises one or more selected from cyclodextrin or salts thereof, and the pharmaceutical composition also comprises a nitrite scavenger.

This invention relates to the ability of formula (I) to function as α v Novel compounds of β6 integrin antagonists, their use in treating diseases, methods of their manufacture, and compositions comprising said compounds for this purpose, wherein R 1 Selected from: R 1a 、-C(O)R 1a -C(O)OR 1a -C(O)NHR 1a 、-C(O)N(R 1a )2、-SO2R 1a , where R 1a Each is independently selected from: alkyl, alkenyl, alkynyl, aryl, heteroaryl, alkylaryl, or alkylheteraryl, wherein each can be optionally substituted; R 2 Selected from: hydrogen, halogen, optionally substituted alkyl or optionally substituted alkoxy; R 2a Each is independently selected from: hydrogen, halogen, optionally substituted alkyl or optionally substituted alkoxy; R 3 Selected from: hydrogen, optionally substituted alkyl, or optionally substituted alkoxy; R 4 For hydroxyl group; Ar 1 It is optionally substituted heteroaryl or bicyclic heteroaryl; and L is a linker; or a pharmaceutically acceptable salt thereof.

The invention belongs to the field of medical chemistry, and discloses Ilunocitinib as well as a preparation method and application thereof. 4-pyrazole boronic acid pinacol ester (I) is used as an initial raw material, the initial raw material and 3-(cyanomethylene) azetidine-1-tert-butyl formate (II) are subjected to a Michael addition reaction to prepare a compound III, and the compound III and the compound IV are subjected to a catalytic coupling reaction to prepare a compound V; removing a Boc protecting group from the compound V under an acidic condition to prepare a compound VI; carrying out sulfonamide reaction on the compound VI and cyclopropyl sulfonyl chloride in an organic solvent to obtain a compound VII; and removing a protecting group from the compound VII under an alkaline condition to obtain a final product Ilunocitinib. The preparation method of the Ilunociitinib has the advantages that the raw materials are easy to obtain, the process is simple, the operation is convenient, the reaction yield is higher than that recorded in the existing literature, and the industrial production is easy.

The invention provides a benzo ring type carbon dioxide-philic microsphere as well as a preparation method and application thereof. The preparation method of the benzo ring type carbon dioxide-philic microspheres comprises the following steps: mixing acrylamide, a benzo ring monomer, a propanesulfonic acid monomer and a cross-linking agent, and carrying out polymerization reaction under the action of an initiator; wherein the benzoring monomer comprises one or a combination of more than two of 4-vinyl benzocyclobutene, benzoazetidine, benzoxetane, benzothietane, 2, 3-indoline, 2, 3-dihydrobenzofuran and 2, 3-dihydrobenzothiophene, and the benzoring monomer comprises one or a combination of more than two of 4-vinyl benzocyclobutene, benzoazetidine, benzoxetane, benzothietane, 2, 3-indoline, 2, 3-dihydrobenzofuran and 2, 3-dihydrobenzothiophene. The mass ratio of the acrylamide to the benzo ring monomer to the propanesulfonic acid monomer is (5-20): (0.08-0.8): (0.4-1.6); the temperature of the polymerization reaction is 30-55 DEG C, and the time is 6-10 hours. The microsphere material can form a high-strength three-dimensional network, and in-situ physical plugging of a gas channeling channel is achieved.

This invention discloses a high-throughput synthesis method for 1-phenylazine heterocyclic butane compounds, comprising the following steps: in a solvent, the compound shown in Formula I and the compound shown in Formula II undergo a C-N coupling reaction in the presence of a catalyst and a base to obtain the 1-phenylazine heterocyclic butane compound shown in Formula III; wherein, R1 and R2 are any one of alkyl, halogen, aryl, substituted aryl, alkoxy, hydroxy, and nitrile groups; R3 is any one of F, Cl, Br, and I; and R4 is any one of hydroxyl, alkyloxy, H, halogen, and alkyl groups. This invention constructs a series of nitrogen heterocyclic compounds through high-throughput synthesis, obtaining a series of nitrogen heterocyclic compounds, and, through appropriate high-throughput screening, obtains the optimal reaction conditions in a very short time, thus solving the problems of the complexity of constructing carbon-nitrogen heterocycles and the difficulty in selecting conditions, as well as the high labor and time costs associated with existing synthetic methods.

The application discloses the development of scalable thiol reactivity (STRP), a method which enables the facile interrogation of large chemical libraries for intrinsic reactivity with cysteine. The application further discloses high throughput screening assays using STRP identified azetidinyl oxadiazole as a moiety that selectively reacts with cysteine through a ring opening-based mechanism, capable of covalently engaging cysteine residues broadly across the human proteome. The application further discloses an azetidinyl oxadiazole containing small molecule that augments the catalytic activity of the deubiquitinase UCHL1 in vitro and in cells by covalently modifying a cysteine distal to its enzymatic active site.

The present invention relates to novel antagonists of the A2B adenosine receptor and pharmaceutical compositions comprising said antagonists as well as their uses for the treatment and prevention of disorders known to be susceptible to improvement by antagonism of the A2B receptor such as asthma, chronic obstructive pulmonary disorder (COPD), pulmonary fibrosis, vascular diseases, allergic diseases, hypertension, retinopathy, diabetes mellitus, inflammatory gastrointestinal tract disorders, inflammatory diseases, autoimmune diseases, renal diseases, neurological disorders and, in particular, cancers. In particular, the present invention relates to compounds of formula (I), wherein R1 represents 1 to 3 identical or different R1 substituents, wherein said R1 is independently at each occurrence selected from hydrogen, halogen, C1-C8alkyl, C1-C8haloalkyl, C1-C8alkoxy, C1-C8hydroxyalkyl and C1-C8alkoxyalkyl; Ra is selected from phenyl, pyridinyl, pyrimidinyl, thiazolyl, thiodiazolyl, oxazolyl, pyrazolyl and triazolyl wherein said phenyl, pyridinyl, thiazolyl, thiodiazolyl, oxazolyl, pyrazolyl and triazolyl is independently optionally substituted by one or more substituents independently selected from halogen, hydroxyl, cycloalkyl, C1-C4alkyl-substituted cycloalkyl, C1-C8alkyl, C1-C8haloalkyl, C1-C8alkoxy, C1-C8alkylaminocarbonyl, C1-C8hydroxyalkyl, C1-C8dialkylaminoC1-C8alkyl, C1-C8aminoalkyl and a heterocycle selected from oxiran, oxetane, aziridine and azetidine wherein said oxiran, oxetane, aziridine and azetidine are independently optionally substituted by halogen, hydroxyl, C1-C4alkyl, C1-C2haloalkyl, C1-C2alkoxy; or Ra is —CONHR′ wherein R′ is selected from C1-C8alkyl, cycloalkyl, aryl, heteroaryl and C1-C8alkyl-N-morpholino, wherein said aryl, heteroaryl and C1-C8alkyl-N-morpholino is independently optionally substituted by [one or more] substituents selected from halogen, cycloalkyl, C1-C8alkyl, C1-C8alkoxy, C1-C8hydroxalkyl and C1-C8alkoxyalkyl; Ar / Het is selected from pyridinyl, phenyl and oxazolyl wherein said pyridinyl, phenyl and oxazolyl is independently optionally substituted by one or more substituents independently selected from halogen, cyano, C1-C8alkyl, C1-C8haloalkyl, C1-C8alkoxy, C1-C8hydroxyalkyl and C1-C8alkoxyalkyl; or pharmaceutically acceptable salt, or hydrate thereof.

The present invention relates to formulations of farnesol X receptor agonists. Specifically, described herein are pharmaceutical formulations of the farnesoid X receptor agonist 3-hydroxyazetidine-trans-1-carboxylic acid 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl) pyridin-2-yl) ((4-(4-methoxy-3-methylphenyl) bicyclo [2.2. 2] octane-1-yl) methyl) carbamoyl) cyclohexyl, and methods for preparing the pharmaceutical formulations of the farnesoid X receptor agonist 3-hydroxyazetidine-trans-1-carboxylic acid. And methods of treating conditions, diseases, or conditions associated with farnesoid X receptor activity using such pharmaceutical formulations.

This invention relates to a method for preparing impurity A-7-imp3 and its uses. The significance of this invention lies in guiding the improvement of the process for (6-(4-((4-(1H-pyrazol-4-yl)phenyl)amino)pyrimidin-2-yl)-1-methyl-1H-indol-2-yl)(3,3-difluoroazacyclobutane-1-yl)methyl ketone (Formula A), thereby enhancing product quality, making product quality more controllable, and ensuring greater safety of the drug.

The present invention relates to novel antagonists of the A2B adenosine receptor and pharmaceutical compositions comprising said antagonists as well as their uses for the treatment and prevention of disorders known to be susceptible to improvement by antagonism of the A2B receptor such as asthma, chronic obstructive pulmonary disorder (COPD), pulmonary fibrosis, vascular diseases, allergic diseases, hypertension, retinopathy, diabetes mellitus, inflammatory gastrointestinal tract disorders, inflammatory diseases, autoimmune diseases, renal diseases, neurological disorders and, in particular, cancers.In particular, the present invention relates to compounds of formula IwhereinR1 represents 1 to 3 identical or different R1 substituents, wherein said R1 is independently at each occurrence selected from hydrogen, halogen, C1-C8alkyl, C1-C8haloalkyl, C1-C8alkoxy, C1-C8hydroxyalkyl and C1-C8alkoxyalkyl; Ra is selected from phenyl, pyridinyl, pyrimidinyl, thiazolyl, thiodiazolyl, oxazolyl, pyrazolyl and triazolyl wherein said phenyl, pyridinyl, thiazolyl, thiodiazolyl, oxazolyl, pyrazolyl and triazolyl is independently optionally substituted by one or more substituents independently selected from halogen, hydroxyl, cycloalkyl, C1-C4alkyl-substituted cycloalkyl, C1-C8alkyl, C1-C8haloalkyl, C1-C8alkoxy, C1-C8alkylaminocarbonyl, C1-C8hydroxyalkyl, C1-C8dialkylaminoC1-C8alkyl, C1-C8aminoalkyl and a heterocycle selected from oxiran, oxetane, aziridine and azetidine wherein said oxiran, oxetane, aziridine and azetidine are independently optionally substituted by halogen, hydroxyl, C1-C4alkyl, C1-C2haloalkyl, C1-C2alkoxy; or Ra is —CONHR′ wherein R′ is selected from C1-C8alkyl, cycloalkyl, aryl, heteroaryl and C1-C8alkyl-N-morpholino, wherein said aryl, heteroaryl and C1-C8alkyl-N-morpholino is independently optionally substituted by [one or more] substituents selected from halogen, cycloalkyl, C1-C8alkyl, C1-C8alkoxy, C1-C8hydroxalkyl and C1-C8alkoxyalkyl;Ar / Het is selected from pyridinyl, phenyl and oxazolyl wherein said pyridinyl, phenyl and oxazolyl is independently optionally substituted by one or more substituents independently selected from halogen, cyano, C1-C8alkyl, C1-C8haloalkyl, C1-C8alkoxy, C1-C8hydroxyalkyl and C1-C8alkoxyalkyl;or pharmaceutically acceptable salt, or hydrate thereof.