882272-97-1

Upstream product

• 4316-93-2 4,6-dichloro-5-nitropyrimidine 
• 103-49-1 dibenzylamine 

Downstream Products

• 1351636-67-3 tert-butyl 3-{[6-(dibenzylamino)-5-nitropyrimidin-4-yl]amino}azetidine-1-carboxylate 
• 1448444-79-8 tert-butyl 4-(6-(dibenzylamino)-5-nitropyrimidin-4-ylamino)phenyl(methyl)carbamate 
• 1448444-48-1 tert-butyl 3-(5-amino-6-(dibenzylamino)pyrimidin-4-ylamino)phenylcarbamate 
• 1448444-47-0 tert-butyl 3-(6-(dibenzylamino)-5-nitropyrimidin-4-ylamino)phenylcarbamate 
• 1351636-74-2 tert-butyl (3R)-3-{[6-(dibenzylamino)-5-nitropyrimidin-4-yl]amino} pyrrolidine-1-carboxylate 
• 1610473-66-9 tert-butyl 3-(6-(dibenzylamino)-8-oxo-7H-purin-9(8H)-yl)pyrrolidine-1-carboxylate 
• 1610473-65-8 tert-butyl 3-(5-amino-6-(dibenzylamino)pyrimidin-4-ylamino)pyrrolidine-1-carboxylate 
• 1610473-61-4 (S)-tert-butyl 2-((6-(dibenzylamino)-8-oxo-7H-purin-9(8H)-yl)methyl)pyrrolidine-1-carboxylate 
• 1610473-60-3 (S)-tert-butyl 2-((5-amino-6-(dibenzylamino)-pyrimidin-4-ylamino)methyl)pyrrolidine-1-carboxylate 
• 1610473-64-7 tert-butyl 3-(6-(dibenzylamino)-5-nitropyrimidin-4-ylamino)pyrrolidine-1-carboxylate 
• 1610473-59-0 (S)-tert-butyl 2-((6-(dibenzylamino)-5-nitropyrimidin-4-ylamino)methyl)pyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

HCK AS A THERAPEUTIC TARGET IN MYD88 MUTATED DISEASES

The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., HCK, BTK, LYN, BLK, FRK) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating diseases (e.g., proliferative diseases) in a subject in need thereof).

CYCLOALKYLIDENE CARBOXYLIC ACIDS AND DERIVATIVES AS BTK INHIBITORS

The present invention relates to novel cycloalkylidene carboxylic acids and derivatives thereof useful as Bruton tyrosine kinase (BTK) inhibitors. The present disclosure also relates to processes for their preparation, pharmaceutical compositions containing one or more such compounds, and to the use of such compounds and pharmaceutical compositions for the treatment of disorders involving mediation of BTK in humans (Formula I).

COMPOUNDS USEFUL AS KINASE INHIBITORS

Provided are certain BTK inhibitors, pharmaceutical compositions thereof, and methods of use thereof.

Therapeutic Combinations of a Proteasome Inhibitor and a BTK Inhibitor

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.

INHIBITORS OF BRUTON'S TYROSINE KINASE

Inhibitors for Bruton's Tyrosine Kinase (BTK) are disclosed as are compositions thereof, methods for their preparation, and methods for their use.

THERAPEUTIC COMBINATIONS OF A CD19 INHIBITOR AND A BTK INHIBITOR

Therapeutic combinations of a CD 19 inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a CD 19 inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer, such as a hematological malignancy. A combination of a BTK inhibitor and a CD 19 inhibitor, such as a CD19-targeted antibody or a CD19-targeted chimeric antigen receptor expressing T cell or NK cell, and compositions and uses thereof are disclosed. Combinations of a BTK inhibitor and a CD 19 inhibitor with a programmed death- 1 (PD-1) or PD-1 ligand (PD-L1) inhibitor and compositions and uses thereof are also disclosed.

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.

NOVEL HYDRAZINO COMPOUNDS AS BTK INHIBITORS

The present invention relates to novel hydrazino compounds of Formula (I) as Bruton tyrosine kinase inhibitors, process of preparation thereof, and to the use of the compounds in the preparation of pharmaceutical compositions for the therapeutic treatment of disorders involving mediation of Bruton tyrosine kinase in humans.

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.