1351636-18-4

Basic information

• Product Name: Btk Kinase inhibitor
• Synonyms: Btk Kinase inhibitor;ONO BTK;ONO-4059(GS-4059,Tirabrutinib) free base;6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one;Tirabrutinib (ONO-4059)
• CAS NO: 1351636-18-4
• Molecular Formula: C₂₅H₂₂N₆O₃
• Molecular Weight: 454.48058
• Mol File: 1351636-18-4.mol

Chemical Properties

• Boiling Point: 672.0±65.0 °C(Predicted)
• Appearance: /
• Density: 1.412±0.06 g/cm3(Predicted)
• PKA: 3.16±0.20(Predicted)
• CAS DataBase Reference: Btk Kinase inhibitor(CAS DataBase Reference)
• NIST Chemistry Reference: Btk Kinase inhibitor(1351636-18-4)
• EPA Substance Registry System: Btk Kinase inhibitor(1351636-18-4)

Safety Data

• Hazardous Substances Data: 1351636-18-4(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Btk Kinase inhibitor is used as a therapeutic agent for the treatment of B-cell cancers such as chronic lymphocytic leukemia, mantle cell lymphoma, and non-Hodgkin lymphoma. It works by inhibiting the activity of Bruton’s tyrosine kinase, which is overexpressed or mutated in these diseases, leading to the uncontrolled growth of B cells. This inhibition helps in controlling the progression of the disease and improving patient outcomes.
Used in Autoimmune Diseases:
Btk Kinase inhibitor is used as a treatment option for certain autoimmune diseases where the immune system mistakenly attacks the body's own tissues. By dampening B cell responses, these inhibitors can help in reducing the severity of the disease and managing symptoms. The inhibition of Bruton’s tyrosine kinase is crucial in this context, as it plays a significant role in the activation and survival of B cells, which are often involved in the pathogenesis of autoimmune disorders.
Used in Drug Development:
Btk Kinase inhibitor is used as a target for the development of new drugs in the pharmaceutical industry. The identification and characterization of Btk inhibitors have opened up new avenues for the treatment of B-cell cancers and autoimmune diseases. Researchers and pharmaceutical companies are actively involved in the discovery and optimization of novel Btk inhibitors to improve their efficacy, safety, and selectivity, ultimately leading to better therapeutic options for patients.

Upstream product

• 1351636-74-2 tert-butyl (3R)-3-{[6-(dibenzylamino)-5-nitropyrimidin-4-yl]amino} pyrrolidine-1-carboxylate 
• 1439901-94-6 tert-butyl (3R)-3-(6-amino-8-oxo-7, 8-dihydro-9H-purin-9-yl)pyrrolidine-1-carboxylate 
• 590-93-2 2-Butynoic acid 

Relevant articles and documents

PROCESS FOR PRODUCING PURINONE DERIVATIVE

According to the present invention, differently from well-known production methods, with the use of a different starting material, Ullmann condensation which may decrease the yield with an increase of a production scale can be avoided and thus 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one can be provided safely and stably with high reaction yield.

Therapeutic Combinations of an IRAK4 Inhibitor and a BTK Inhibitor

Therapeutic combinations of an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an IRAK4 inhibitor and a BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

BTK INHIBITORS TO TREAT SOLID TUMORS THROUGH MODULATION OF THE TUMOR MICROENVIRONMENT

In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR

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.

THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR

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 OF TREATING CANCERS, IMMUNE AND AUTOIMMUNE DISEASES, AND INFLAMMATORY DISEASES BASED ON BTK OCCUPANCY AND BTK RESYNTHESIS RATE

In an embodiment, therapeutic methods and use of a Bruton's Tyrosine Kinase (BTK) inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.

METHODS OF BLOCKING THE CXCR-4/SDF-1 SIGNALING PATHWAY WITH INHIBITORS OF BRUTON'S TYROSINE KINASE

In some embodiments, the present invention relates to novel small molecule inhibitors that block the CXCR4-SDF-1 signaling pathway by directly inhibiting members of the Tec family of kinases, namely Bruton's tyrosine kinase (BTK), and their use in treating diseases in which pathogenesis is mediated by the CXCR4/SDF-1 signaling pathway.

METHODS OF BLOCKING THE CXCR-4/SDF-1 SIGNALING PATHWAY WITH INHIBITORS OF BONE MARROW X KINASE

In some embodiments, the present invention relates to novel small molecule inhibitors that block the CXCR4-SDF-1 signaling pathway by directly inhibiting members of the Tec family of kinases, namely bone marrow X kinase (BMX) (also known as epithelial and endothelial tyrosine kinase (ETK)), and their use in treating diseases in which pathogenesis is mediated by the CXCR4/SDF-1 signaling pathway.

PURINONE DERIVATIVE HYDROCHLORIDE

The purinone derivative 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one hydrochloride has Btk-selective inhibitory activity and, in addition to having excellent metabolic stability, it is a compound that exhibits a high level of solubility and absorption with respect to the free base and can be crystallized, hence it can serve as a therapeutic agent for diseases involving B cells and mast cells.

PURINONE DERIVATIVE

Compounds represented by general formula (I) (all of the symbols in the formula conform to the definitions in the Description) are compounds that, in addition to having a Btk-selective inhibitory activity, exhibit an excellent metabolic stability and can avoid hepatotoxicity or the like, and as a consequence can provide safe therapeutic agents for diseases in which B cells or mast cells participate.