78 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 I

and 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.

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; R_a is H or —CH₃; each R_b 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.

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 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.

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.

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.

There are provided, inter alia, compositions and methods for treatment of cancer. The methods include administering to a subject in need a therapeutically effective amount of a Bruton's tyrosine kinase (BTK) antagonist and a ROR-1 antagonist. Further provided are pharmaceutical compositions including a BTK antagonist, ROR-1 antagonist and a pharmaceutically acceptable excipient. In embodiments, the BTK antagonist is ibrutinib and the ROR-1 antagonist is cirmtuzumab.