1231891-09-0Relevant articles and documents
Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)
De Lucca, George V.,Shi, Qing,Liu, Qingjie,Batt, Douglas G.,Beaudoin Bertrand, Myra,Rampulla, Rick,Mathur, Arvind,Discenza, Lorell,D'Arienzo, Celia,Dai, Jun,Obermeier, Mary,Vickery, Rodney,Zhang, Yingru,Yang, Zheng,Marathe, Punit,Tebben, Andrew J.,Muckelbauer, Jodi K.,Chang, Chiehying J.,Zhang, Huiping,Gillooly, Kathleen,Taylor, Tracy,Pattoli, Mark A.,Skala, Stacey,Kukral, Daniel W.,McIntyre, Kim W.,Salter-Cid, Luisa,Fura, Aberra,Burke, James R.,Barrish, Joel C.,Carter, Percy H.,Tino, Joseph A.
, p. 7915 - 7935 (2016)
Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.
