1108745-35-2Relevant academic research and scientific papers
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
Menichincheri, Maria,Ardini, Elena,Magnaghi, Paola,Avanzi, Nilla,Banfi, Patrizia,Bossi, Roberto,Buffa, Laura,Canevari, Giulia,Ceriani, Lucio,Colombo, Maristella,Corti, Luca,Donati, Daniele,Fasolini, Marina,Felder, Eduard,Fiorelli, Claudio,Fiorentini, Francesco,Galvani, Arturo,Isacchi, Antonella,Borgia, Andrea Lombardi,Marchionni, Chiara,Nesi, Marcella,Orrenius, Christian,Panzeri, Achille,Pesenti, Enrico,Rusconi, Luisa,Saccardo, Maria Beatrice,Vanotti, Ermes,Perrone, Ettore,Orsini, Paolo
, p. 3392 - 3408 (2016/05/19)
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
Orsini, Paolo,Menichincheri, Maria,Vanotti, Ermes,Panzeri, Achille
body text, p. 3098 - 3100 (2009/10/04)
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
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Page/Page column 74, (2009/03/07)
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.
