1609467-62-0Relevant articles and documents
Aminopyrazole Carboxamide Bruton's Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning
Schnute, Mark E.,Benoit, Stephen E.,Buchler, Ingrid P.,Caspers, Nicole,Grapperhaus, Margaret L.,Han, Seungil,Hotchandani, Rajeev,Huang, Nelson,Hughes, Robert O.,Juba, Brian M.,Kim, Kyung-Hee,Liu, Erica,McCarthy, Erin,Messing, Dean,Miyashiro, Joy S.,Mohan, Shashi,O'Connell, Thomas N.,Ohren, Jeffrey F.,Parikh, Mihir D.,Schmidt, Michelle,Selness, Shaun R.,Springer, John R.,Thanabal, Venkataraman,Trujillo, John I.,Walker, Daniel P.,Wan, Zhao-Kui,Withka, Jane M.,Wittwer, Arthur J.,Wood, Nancy L.,Xing, Li,Zapf, Christoph W.,Douhan, John
supporting information, p. 80 - 85 (2019/01/15)
Potent covalent inhibitors of Bruton's tyrosine kinase (BTK) based on an aminopyrazole carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive groups leading to irreversible protein adducts, cyanamide-based reversible-covalent inhibitors provided the highest combined BTK potency and EGFR selectivity. The cyanamide covalent mechanism with BTK was confirmed through enzyme kinetic, NMR, MS, and X-ray crystallographic studies. The lead cyanamide-based inhibitors demonstrated excellent kinome selectivity and rat pharmacokinetic properties.
BRUTON'S TYROSINE KINASE INHIBITORS
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, (2014/05/24)
Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)
