72 results about "Bruton's tyrosine kinase inhibitor" patented technology

The invention discloses a Bruton tyrosine kinase inhibitor with spiro or endo structure and a preparation method thereof. The inhibitor comprises Formula (I). The inhibitor has an obvious inhibiting action on BTK activity, and the inhibition activity for DOHH2 cells is enhanced by approximately 8 times. The spiro or endo compound can be used as a BTK inhibitor, and has wide application prospects in resisting malignant tumors.

The invention relates to a compound with a formula I and a pharmaceutically acceptable salt, a solvent compound, an active metabolite, a polycrystalline compound, an ester, an isomer or a prodrug thereof, a pharmaceutical composition containing the compound in the formula I, and application using the same as a selective Bruton's tyrosine kinase inhibitor to prepare a medicine for preventing or treating heterologous immunity diseases and self immunity diseases or cancers. The formula is shown in the specification.

Therapeutic combinations of a proteasome inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a proteasome inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.

The invention provides a double-site irreversible Brutons tyrosine kinase inhibitor, a drug combination containing the same and application thereof to the anti-tumor field. The compound provided by the invention has an anti-proliferation inhibiting effect to tumor cell stains such as A549, SGC7901, MCF-7, PC-9 and HL-60, and can be applied to drugs for treating solid tumors or blood cancers related to human or animal cell proliferation; the compound provided by the invention has a better pharmacokinetic property and can be applied to treating solid tumors or blood cancers related to human or animal cell proliferation or autoimmune diseases through oral taking; the compound provided by the invention has a double-site response characteristic.

This invention relates to compounds of formula (I). The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.

This invention relates to compounds of formula (I). The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.

Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.

The invention relates to a compound with a structure shown in a formula I or a pharmaceutically acceptable salt, a solvate, an active metabolite, a polymorphic substance, an ester, an optical isomer or a prodrug, a pharmaceutical composition comprising the compound with the structure shown in the formula I, and application of the pharmaceutical composition as a bruton tyrosine kinase inhibitor topreparing a medicine for preventing or treating various immune diseases, autoimmune diseases or cancers.

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and / or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

Methods to improve hematopoiesis and increase white blood cell counts in subjects and patients using pyrimidine-based inhibitors of Bruton's tyrosine kinase (Btk) are disclosed.

Disclosed are histone deacetylase (HDAC) inhibitors, or combinations comprising an HDAC inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of chronic lymphocytic leukemia in a subject in need thereof. Also provided herein are methods for treating chronic lymphocytic leukemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an HDAC inhibitor, or a combination comprising an HDAC inhibitor and a BTK inhibitor. Other related methods are disclosed.

Methods to improve hematopoiesis and increase white blood cell counts in subjects and patients using pyrimidine-based inhibitors of Bruton's tyrosine kinase (Btk) are disclosed.

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.

Therapeutic combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a BTK inhibitor, and methods of treating a disease using a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, and methods of treating a disease using a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease.

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 describes a pharmaceutical combination of an anti-CD19 antibody and a Bruton's tyrosine kinase (BTK) inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia.

The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.

The invention relates to the field of drug synthesis, specifically to a preparation method of a Bruton's tyrosine kinase inhibitor. The new method comprises: carrying out a dark reaction between 4-amino-3-(4-phenoxylphenyl)-1H-pyridino(3,4-d)pyrimidine and (S)-tert-butoxycarbonyl-3-hydroxy piperidine in the action of triphenyl phosphine and diisopropyl azodiformate, taking Boc off in an acidic condition to form salt, performing crystallization with 25% NaOH to dissolve salt to prepare an intermediate I in one pot, and reacting the intermediate I with acryloyl chloride in an alkaline condition to generate a target product. The preparation method is simple in production condition, low in cost and high in yield, is eco-friendly and clean, and is suitable for industrial production.

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and / or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

This disclosure relates to the field of therapeutic tyrosine kinase inhibitors, in particular Bruton tyrosine kinase (“BTK”) inhibitors for treatment of subjects with relapsing multiple sclerosis.

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase-4 / 6 (CDK4 / 6) inhibitor, and / or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4 / 6 (CDK4 / 6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.

The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR′R″, C(O)NR′R″, C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR′R″, hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR′R″, C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R′ and R″ is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of thefragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl,non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula I or pharmaceutically acceptable salts thereof. Formula I or a pharmaceutically acceptable salt thereof or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds in the treatment of Btk mediated disorders.

Disclosed herein are protein kinase inhibitors, in particular Bruton's tyrosine kinase (BTK) inhibitors, pharmaceutical compositions comprising them, processes for preparing them and uses of such protein kinase inhibitors to treat or prevent diseases, disorders and conditions associated with kinase function. In particular, the present invention relates to selective BTK inhibitors.

The present invention relates to pyrazole fused-ring derivatives, their preparation methods, and use thereof in medicine. In particular, the present invention relates to a novel derivative represented by formula (I), and a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising the same and a method for preparing the same. The present invention also relates to use of the derivatives and the pharmaceutically acceptable salt thereof or the pharmaceutical composition comprising the same in the preparation of therapeutic agents, in particular Bruton tyrosine kinase inhibitors, and preparing a medicament for treating and / or preventing tumors and inflammatory associated diseases. The substituents on formula (I) are defined same as in the specification.