1242156-60-0Relevant articles and documents
Finding the perfect spot for fluorine: Improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold
Lou, Yan,Sweeney, Zachary K.,Kuglstatter, Andreas,Davis, Dana,Goldstein, David M.,Han, Xiaochun,Hong, Junbae,Kocer, Buelent,Kondru, Rama K.,Litman, Renee,McIntosh, Joel,Sarma, Keshab,Suh, Judy,Taygerly, Joshua,Owens, Timothy D.
, p. 367 - 371 (2015/02/19)
A rational fluorine scan based on co-crystal structures was explored to increase the potency of a series of selective BTK inhibitors. While fluorine substitution on a saturated bicyclic ring system yields no apparent benefit, the same operation on an unsaturated bicyclic ring can increase HWB activity by up to 40-fold. Comparison of co-crystal structures of parent molecules and fluorinated counterparts revealed the importance of placing fluorine at the optimal position to achieve favorable interactions with protein side chains.
8-FLUOROPHTHALAZIN-1(2H)-ONE COMPOUNDS
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, (2013/05/21)
8-Fluorophthalazin-1(2h)-one compounds of Formula II where one or two of X1, X2, and X3 are N, are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula II for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
