1268830-75-6Relevant academic research and scientific papers
COMPOUNDS FOR THE TREATMENT OF BRAF-ASSOCIATED DISEASES AND DISORDERS
-
, (2021/01/20)
Provided herein are compounds of the Formula I: and pharmaceutically acceptable salts, solvates and polymorphs thereof, wherein L, X1, R1, R2, R3, R4, R5 and R6 are as defined herein, for the treatment of BRAF-associated diseases and disorders, including BRAF-associated tumors, including malignant and benign BRAF-associated tumors of the CNS and malignant extracranial BRAF-associated tumors.
HETEROCYCLIC SULFONAMIDES AS RAF INHIBITORS
-
, (2012/09/21)
Compounds of Formula (I) are useful for inhibition of Raf kinases. Methods of using compounds of Formula (I), stereoisomers, tautomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
Potent and selective aminopyrimidine-based B-Raf inhibitors with favorable physicochemical and pharmacokinetic properties
Mathieu, Simon,Gradl, Stefan N.,Ren, Li,Wen, Zhaoyang,Aliagas, Ignacio,Gunzner-Toste, Janet,Lee, Wendy,Pulk, Rebecca,Zhao, Guiling,Alicke, Bruno,Boggs, Jason W.,Buckmelter, Alex J.,Choo, Edna F.,Dinkel, Victoria,Gloor, Susan L.,Gould, Stephen E.,Hansen, Joshua D.,Hastings, Gregg,Hatzivassiliou, Georgia,Laird, Ellen R.,Moreno, David,Ran, Yingqing,Voegtli, Walter C.,Wenglowsky, Steve,Grina, Jonas,Rudolph, Joachim
, p. 2869 - 2881 (2012/06/01)
Recent clinical data provided proof-of-concept for selective B-Raf inhibitors in treatment of B-RafV600E mutant melanoma. Pyrazolopyridine-type B-Raf inhibitors previously described by the authors are potent and selective but exhibit low solubility requiring the use of amorphous dispersion-based formulation for achieving efficacious drug exposures. Through structure-based design, we discovered a new class of highly potent aminopyrimidine-based B-Raf inhibitors with improved solubility and pharmacokinetic profiles. The hinge binding moiety possesses a basic center imparting high solubility at gastric pH, addressing the dissolution limitation observed with our previous series. In our search for an optimal linker-hinge binding moiety system, amide-linked thieno[3,2-d]pyrimidine analogues 32 and 35 (G945), molecules with desirable physicochemical properties, emerged as lead compounds with strong efficacy in a B-RafV600E mutant mouse xenograft model. Synthesis, SAR, lead selection, and evaluation of key compounds in animal studies will be described.
RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF
-
, (2011/04/14)
Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF
-
, (2011/04/14)
Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or trea
RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF
-
, (2011/04/14)
Compounds of Formula II are useful for inhibition of Raf kinases. Methods of using compounds of Formula II and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or tr
RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF
-
, (2011/04/14)
Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or trea
