1108745-32-9

Upstream product

• 1108745-27-2 2-fluoro-5-(5-fluoro-2-methyl-benzyl)-benzonitrile 
• 218301-22-5 2-fluoro-5-formylbenzonitrile 
• 163517-62-2 (5-fluoro-2-methylphenyl)boronic acid 
• 261951-71-7 2-(bromomethyl)-4-fluoro-1-methylbenzene 
• 214210-21-6 3-cyano-4-fluorophenylboronic acid 

Downstream Products

• 1108743-88-9 N-[5-(2-methyl-5-fluoro-benzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide 

Relevant academic research and scientific papers

Preparation method of 5-benzyl-1H-indazole-3-amine compound

The invention discloses a method for preparing a 5-benzyl-1H-indazole-3-amine compound and a preparation method of the 5-benzyl-1H-indazole-3-amine compound. According to the method, 2-fluoro-5-formyl cyanophenyl, p-toluenesulfonhydrazide and arylboronic acid are taken as substrates and react in 1, 4-dioxane in the presence of alkali, and the 2-fluoro-5-benzyl cyanophenyl compound is obtained. The preparation method comprises the following steps: dissolving a 2-fluoro-5-benzyl cyanophenyl compound and hydrazine hydrate in tert-butyl alcohol, and reacting to obtain the 5-benzyl-1H-indazole-3-amine compound. The method provided by the invention has the following characteristics: (1) the reaction raw materials are common commercial raw materials, and the used alkali and solvent are cheap and easy to obtain; no noble metal catalyst is used, and the production cost is low; (2) the reaction is insensitive to air and moisture, and the open reaction has no influence on the yield; magnesium powder is not used as a Grignard reagent, water and oxygen removal operation is not needed, and the method is safe, efficient and suitable for industrial production; and (3) treatment and purification after reaction are simple and convenient, and pollution of solvents and silica gel to the environment is reduced.

Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase responsible for the development of different tumor types. Despite the remarkable clinical activity of crizotinib (Xalkori), the first ALK inhibitor approved in 2011, the emergence of resistance mutations and of brain metastases frequently causes relapse in patients. Within our ALK drug discovery program, we identified compound 1, a novel 3-aminoindazole active on ALK in biochemical and in cellular assays. Its optimization led to compound 2 (entrectinib), a potent orally available ALK inhibitor active on ALK-dependent cell lines, efficiently penetrant the blood-brain barrier (BBB) in different animal species and highly efficacious in in vivo xenograft models. Moreover, entrectinib resulted to be strictly potent on the closely related tyrosine kinases ROS1 and TRKs recently found constitutively activated in several tumor types. Entrectinib is currently undergoing phase I/II clinical trial for the treatment of patients affected by ALK-, ROS1-, and TRK-positive tumors.

Highly efficient synthesis of 5-benzyl-3-aminoindazoles

A rapid and efficient procedure for the preparation of 5-benzyl-3-aminoindazoles 1 is reported. Key intermediates are fluoro-cyano diarylmethanes 2 which have been obtained by two different synthetic approaches. Benefits of these methods result from the u

SUBSTITUTED INDAZOLE DERIVATIVES ACTIVE AS KINASE INHIBITORS

Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.