1691249-45-2

Basic information

• Product Name: Zanubrutinib
• Synonyms: Zanubrutinib
• CAS NO: 1691249-45-2
• Molecular Formula: C₂₇H₂₉N₅O₃
• Molecular Weight: 471.55086
• EINECS: -0
• Product Categories: API
• Mol File: 1691249-45-2.mol

Chemical Properties

• Boiling Point: 713.4±60.0 °C(Predicted)
• Appearance: /
• Density: 1.33±0.1 g/cm3(Predicted)
• PKA: 15.35±0.40(Predicted)
• CAS DataBase Reference: Zanubrutinib(CAS DataBase Reference)
• NIST Chemistry Reference: Zanubrutinib(1691249-45-2)
• EPA Substance Registry System: Zanubrutinib(1691249-45-2)

Safety Data

• Hazardous Substances Data: 1691249-45-2(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Zanubrutinib is used as an anticancer agent for the treatment of adults with mantle cell lymphoma (MCL), a rare and aggressive type of non-Hodgkin lymphoma. It works by inhibiting the BTK enzyme, which is overactive in MCL cells, leading to the suppression of tumor growth and improved patient outcomes. Zanubrutinib has demonstrated significant clinical benefits in patients with MCL, including those who have relapsed or are refractory to previous treatments.
Additionally, Zanubrutinib is being investigated for its potential use in other B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and Waldenstr?m's macroglobulinemia (WM), due to its ability to target the BTK pathway, which is also dysregulated in these diseases. As a result, Zanubrutinib may offer a promising therapeutic option for patients with these conditions, particularly those who have not responded well to existing treatments.

Upstream product

• 814-68-6 acryloyl chloride 
• 330792-70-6 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile 
• 79-10-7 acrylic acid 
• 1633350-06-7 7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide 

Relevant articles and documents

Preparation method of BTK inhibitor and intermediate thereof

The invention relates to a preparation method of (S)-7-(1-acryloyl piperidine-4-yl)-2-(4-phenoxy phenyl)-4, 5, 6, 7-tetrahydropyrazolo[1, 5-a]pyrimidine-3-formamide and an intermediate thereof.

Method for preparing BTK inhibitor (by machine translation)

The invention relates to a method BTK for preparing. inhibitor, of which is obtained by,step reaction of an easily available,price intermediate 5 to obtain a target product. (by machine translation)

Novel method for synthesizing Zanubrutinib

The invention relates to a novel method for synthesizing Zanubrutinib. The synthetic route provided by the invention has the characteristics of few reaction steps, high yield, good operability, simpleprocess and the like. The method does not involve low-temperature reactions, and can effectively realize industrial large-scale production.

Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase

Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.

TREATMENT OF INDOLENT OR AGGRESSIVE B-CELL LYMPHOMAS USING A COMBINATION COMPRISING BTK INHIBITORS

Disclosed herein is a method for the prevention, delay of progression or treatment of indolent or aggressive B-cell lymphomas in an individual in need thereof, comprising administering a Btk inhibitor (in particularly (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo-[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof) in combination with an anti-PD-1 antibody. The potent and selective BTK inhibitor in combination with the anti-PD-1 antibody have a manageable toxicity profile in patients with indolent and aggressive lymphomas.

USE OF A COMBINATION COMPRISING A BTK INHIBITOR FOR TREATING CANCERS

A method for the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject in need thereof a Btk inhibitor, particularly, (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor or a targeted therapy agent. A pharmaceutical combination comprising a Btk inhibitor, particularly, (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor or a targeted therapy agent.

CRYSTALLINE FORM OF (S)-7-(1-ACRYLOYLPIPERIDIN-4-YL)-2-(4-PHENOXYPHENYL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE, PREPARATION, AND USES THEREOF

The present invention relates to a crystalline form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide for inhibiting Btk, methods of preparation thereof and pharmaceutical compositions, and use of the crystalline form above in the treatment of a disease, or in the manufacturing of a medicament for the treatment of a disease.

FUSED HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS

The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton’ s tyrosine kinase (Btk), and for treating disorders mediated thereby.

FUSED HETEROCYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS

The invention is fused heterocyclic compounds of formula (I), and salts thereof, compositions thereof, and methods of use therefor. In particular, disclosed herein are certain fused heterocyclic compounds that can be useful for inhibiting protein kinase, including Bruton's tyrosine kinase (Btk), and for treating disorders mediated thereby.