81 results about "Bruton's tyrosine kinase" patented technology

Compounds of Formula I-a and all pharmaceutically-acceptable forms thereof, are described herein. The variables R1, R2, R3, Z1, Q, and A shown in Formula I-a are defined herein. Pharmaceutical compositions containing one or more compounds of Formula I-a, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and / or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I-a effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and / or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases. Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity. Methods of treatment include administering a compound of Formula I-a as a single active agent or administering a compound of Formula I-a in combination with one or more other therapeutic agent. A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I-a under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

Compounds of Formula Iand all pharmaceutically acceptable forms thereof, are described herein.The variables R1, R2, R3, Z2, and Q, shown in Formula I are defined herein.Pharmaceutical compositions containing one or more compounds of Formula I, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein.Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and / or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and / or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases.Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity.Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agent.A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. In preferred embodiments, the present invention describes irreversible kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.

The invention relates to a compound for inhibiting the activity of BTK (Bruton's Tyrosine Kinase) and / or JAK3 (Janus Tyrosine Kinase 3), a medicinal composition of the compound, a use of the compound in the pharmacy, a method for inhibiting the activity of BTK and / or JAK3 by using the compound, and a method for treating and / or preventing BTK and / or JAK3 mediated diseases or illnesses in mammals (especially human beings) by using the compound. The compound is represented by structural formula I shown in the specification.

The invention relates to a compound for inhibiting kinase activity of BTK and / or JAK3, as well as a pharmaceutical composition of the compound use of the compound in pharmaceuticals, a method for inhibiting the activity of BTK and / or JAK3 by virtue of the compound and a method for treating and / or preventing BTK and / or JAK3 mediated diseases or symptoms of mammals (particularly human) by virtue of the compound. The compound has a structural formula I shown in the specification.

The present invention relates to heterocyclic compounds of the general formula (I) their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, and polymorphs. The invention also relates to processes for the preparation of the compounds of invention, pharmaceutical compositions containing the compounds and their use as selective Bruton's Tyrosine Kinase (BTK) inhibitors.

The invention provides a series of new multi-fluorine-substituted pyrazolopyrimidine type compounds or salts. The compounds are Bruton's tyrosine kinase (BTK) inhibitors, and can have better kinase inhibition selectivity and pharmacokinetic property. The invention discloses a preparation method of the compounds and also discloses medicine combination containing the compounds with other target medicine compositions or other medicines. The optimized medicine combination has a synergistic effect, can greatly inhibit the existence of tumors as compared with a single target medicine, and can completely eliminate certain tumors. The optimized medicine combination can greatly treat the medicine resistance of the tumors and prevent the cancer recurrence as compared with the single target medicine, and the treatment period is shorter. The invention further relates to combined compounds and medicine preparations using the compounds as active elements, and at a lower dosage, the compounds are safer and have the curative effect of the synergistic effect. The invention further comprises methods for treating and inhibiting the autoimmune diseases or symptoms, heterogeneous immune diseases or symptoms, inflammatory diseases and cancer or symptoms by using the compounds and preparations of the compounds.

Disclosed is a process for the preparation of the following compounds:where R1, R1a and R2a have the definitions in the description, as well as a process to prepare other intermediates that may be useful to synthesise downstream products, especially compounds that are useful as medicaments, for instance Bruton's tyrosine kinase (Btk) inhibitors such as ibrutinib. Also disclosed are other processes, other intermediates and compounds per se.

Disclosed is a process for the preparation of the following compounds:where R1, R1a and R2a have the definitions in the description, as well as a process to prepare other intermediates that may be useful to synthesize downstream products, especially compounds that are useful as medicaments, for instance Bruton's tyrosine kinase (Btk) inhibitors such as ibrutinib. Also disclosed are other processes, other intermediates and compounds per se.

The present invention provides methods of treating, stabilizing or lessening the severity or progression of a disease or disorder associated with BTK.

Disclosed are compounds of Formula (I)wherein: the two dotted lines represent either two single or two double bonds; Q is:R1 is F, Cl, —CN, or —CH3; R2 is Cl or —CH3; R3 is —C(CH3)2OH or —CH2CH2OH; Ra is H or —CH3; each Rb is independently F, Cl, —CH3, and / or —OCH3; and n is zero, 1, or 2. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formula (I)wherein: the two dotted lines represent either two single or two double bonds; Q is:R1 is F, Cl, —CN, or —CH3; R2 is Cl or —CH3; R3 is —C(CH3)2OH or —CH2CH2OH; Ra is H or —CH3; each Rb is independently F, Cl, —CH3, and / or —OCH3; and n is zero, 1, or 2. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Provided are a 2-phenyl-isoquinoline-1-ketone derivative having a structure of formula (I), and uses thereof. The compound has good inhibitory effect on Bruton's tyrosine kinase activity, and the median inhibition concentration of the compound is generally below 10-7 mol.L-1. The compound having the structure of formula (I) and prepared in an embodiment of the present invention has clear anti-inflammatory activity on different animal models.

Compounds of Formula I, as shown below and defined herein:and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).

The present invention provides methods of treating cancer using pyrimidine and pyridine compounds which are inhibitors of Bruton's tyrosine kinase (BTK).

The invention discloses a pyrazolopyrimidine derivative, a preparation method, a pharmaceutical composition and application. The invention provides the pyrazolopyrimidine derivative as shown in a formula I and stereoisomer or solvate or pharmaceutically acceptable salts or active metabolite or prodrug thereof. The pyrazolopyrimidine derivative as shown in the formula I has good inhibitory activity on Bruton's tyrosine kinase (Btk) and particularly has good in vitro and in vivo inhibitory activity on growth of tumor cells, and a good marketization prospect is achieved. Please see the formula I in the description.

The invention discloses a compound with a general formula (I), wherein the compound is capable of inhibiting Btk, and the groups are disclosed in the invention. The compound can be used for treating autoimmune diseases, heterologous immunization diseases, cancers, or thromboembolism diseases. The invention also discloses a pharmaceutical composition containing the compound represented by formula (I). The Bruton's tyrosine kinase inhibitor is capable of inhibiting the activity of Bruton's tyrosine kinas through covalent binding such as a covalent reversible mode.

A method of treating disorders associated with aberrant kinase activity, wherein the kinase is. Adaptor-associated protein kinase 1 (AAK1), Aurora Kinase A (AURKA), Aurora Kinase B (AURKB), Bruton's Tyrosine Kinase (BTK), Interleukin-1 receptor-associated kinase 3 (IRAK3), Protein tyrosine kinase 2 beta (PTK2B), Tyrosine-protein kinase Tec (TEC), Serine / threonine-protein kinase Wee1 (WEE1), Cyclin G-associated kinase (GAK), Large Tumour suppressor 1 Kinase (LATS1), Focal Adhesion Kinase (PTK2), Ribosomal protein S6 kinase alpha-1 (RPS6KA1) said method comprising degrading said kinase.

The present invention provides methods of treating MS using pyrimidine and pyridine compounds which are inhibitors of Bruton's tyrosine kinase (BTK).

The present disclosure provides thiazolyl-containing compounds of Formula (I), (II), or (III). The compounds described herein may be able to inhibit protein kinases (e.g., Src family kinases (e.g., hemopoietic cell kinase (HCK)), Bruton's tyrosine kinase (BTK)) and may be useful in treating and / or preventing proliferative diseases (e.g., myelodysplasia, leukemia, lymphoma (e.g., Waldenstrom's macroglobulinemia)) and in inducing apoptosis in a cell (e.g., malignant blood cell). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

Provided herein are fluorescent lipid binding proteins (FLBPs). The FLBPs comprise a lipid binding domain linked to a fluorophore, whrereby the fluorophore's fluorescence emission undergoes a spectral change upon lipid binding. the fluorophore is selected from the group consisting of 2-dimethylamino-6-acyl-naphthalene (DAN) and RED fluorophore and the lipid binding protein is selected from the group consisting of ENTH domain of epsin 1, C2 domain of bovine lactadherin, C 1B domain of protein kinase C-gamma, C2 domain of cytosolic phospholipase A2-beta, and PH domain of Bruton's tyrosine kinase PH.

The invention relates generally to pharmaceutical tablet compositions comprising fumaric acid and the compound (S)-2-(3′-(hydroxymethyl)-1-methyl-5-((5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)amino)-6-oxo-1,6-dihydro-[3,4′-bipyridin]-2′-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one free base that is an inhibitor of Bruton's tyrosine kinase. The invention further relates to amorphous solid dispersions comprising at least one polymer and the Bruton's kinase inhibitor free base compound. The invention further relates to crystalline mesylate salts, crystalline chloride salts and crystalline sulfate salts of the Bruton's kinase inhibitor free base compound. In some aspects, the crystalline salts are single polymorphs.

The present invention relates to heterocyclic compounds of the general formula (I) their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, and polymorphs. The invention also relates to processes for the preparation of the compounds of invention, pharmaceutical compositions containing the compounds and their use as selective Bruton's Tyrosine Kinase (BTK) inhibitors.

The present invention refers to the synthesis and intermediates of substituted bicyclic compounds by using a central 1H- pyrazolo[3,4-d]pyrimidine of formula (I), which is assembled starting from 4,6-dichloropyrimidine carboxylic acid. The invention in particular refers to the synthesis of the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-l-yl)prop-2-en-l-one(ibrutinib) and its synthesis intermediates.

Compounds of Formula I, as shown below and defined herein:and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).

Crystalline forms of ACP-196, preparation methods, pharmaceutical compositions and uses thereof in the preparation of drugs for treatment and / or prevention of Bruton's tyrosine kinase (BTK)-mediated disorders such as autoimmune diseases or disorders, heteroimmune diseases or disorders, cancers including lymphoma and inflammatory diseases or disorders. As compared with the known solid form of ACP-196, the crystalline forms of the present invention have advantages in crystallinity.

The invention belongs to the field of medicines, and concretely relates to a 4-aminopyrimidine compound having a structural represented by formula (I), or pharmaceutically acceptable salts thereof, a preparation method of the compound, and a use of the compound and the salts as a Bruton tyrosine kinase (BTK) inhibitor. A result of experiments shows that the compound has a significant inhibition effect on the BTK, and can be used for treating thromboembolism, inflammatory disorders, autoimmune diseases, Waldenstrom macroglobulinemia, B cell lymphomas and other diseases.