756509-08-7

Upstream product

• 290835-85-7 2',6'-dichloro-3'-fluoroacetophenone 
• 756520-67-9 (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine 
• 756521-08-1 (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine 
• 756520-66-8 1-(2,6-dichloro-3-fluorophenyl)ethanol 
• 269410-08-4 pyrazole-4-boronic acid pinacol ester 
• 756520-48-6 5-iodo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine 

Downstream Products

• 1023328-06-4 tert-butyl 5-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-N-(benzyloxycarbonyl)-L-norvalinate 
• 1023327-91-4 cyclopentyl 5-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)-ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-N-tert-butoxycarbonyl-L-norvalinate 
• 1023328-07-5 tert-butyl (S)-4-(4-{6-amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-2-benzyloxycarbonylamino-butanoate 
• 877401-42-8 tert-butyl 4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 

Relevant academic research and scientific papers

Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK)

Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.

AMINOHETEROARYL COMPOUNDS AS FOR THE TREATMENT OF DISEASES MEDIATED BY C-MET KINASE ACTIVITY

Compounds of formula (I), are inhibitors of c-Met kinase activity, useful inter alia in the treatment of hyperproliferative diseases: wherein X is -N= or -CH=; ring A is optionally substituted mono- or bi-cyclic aryl or heteroaryl having from 5 to 12 ring

PYRAZOLE-SUBSTITUTED AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS

Compounds of formula (1) are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS

Aminopyridine and aminopyrazine compounds of formula (1), compositions including these compounds, and methods of their use are provided. Preferred compounds of formula 1 have activity as protein kinase inhibitors, including as inhibitors of c-MET.