1. Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup
- Author
-
Tara Renae Rheault, Kimberly N. Smitheman, Kimberly G. Petrov, Chao Han, George Adjabeng, Alex G. Waterson, Marc R. Arnone, Alastair J. King, David E. Uehling, Olivia W. Rossanese, Keith R. Hornberger, Scott Howard Dickerson, John Stellwagen, Cynthia M. Rominger, and Robert A. Mook
- Subjects
Proto-Oncogene Proteins B-raf ,Stereochemistry ,Clinical Biochemistry ,Administration, Oral ,Pharmaceutical Science ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Catalytic Domain ,Drug Discovery ,Animals ,Thiazole ,Protein Kinase Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,Sulfonamides ,Binding Sites ,Kinase ,Chemistry ,Organic Chemistry ,Fluorine ,Rats ,Bioavailability ,Sulfonamide ,Amino Acid Substitution ,Microsomes, Liver ,Molecular Medicine - Abstract
A potent series of inhibitors against the B-RafV600E kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural features of the series are an arylsulfonamide headgroup, a thiazole core, and a fluorine ortho to the sulfonamide nitrogen.
- Published
- 2011
- Full Text
- View/download PDF