Details

Autor(en) / Beteiligte

• 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

Titel

Aminopyrazole Carboxamide Bruton’s Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning

Ist Teil von

• ACS medicinal chemistry letters, 2019-01, Vol.10 (1), p.80-85

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.