Abstract
The discovery of novel pyrazoline derivatives as B-Raf (V600E) inhibitors is described in this report. Chemical modification of the pyrazoline scaffold led to the development of SAR and identified potent and selective inhibitors of B-Raf (V600E). Determination of the pharmacokinetic properties of selected inhibitors is also reported.
2010 Elsevier Ltd. All rights reserved.
MeSH terms
-
Amino Acid Substitution
-
Binding Sites
-
Computer Simulation
-
Drug Evaluation, Preclinical
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry*
-
Protein Kinase Inhibitors / pharmacokinetics
-
Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
-
Proto-Oncogene Proteins B-raf / genetics
-
Proto-Oncogene Proteins B-raf / metabolism
-
Pyrazoles / chemical synthesis
-
Pyrazoles / chemistry*
-
Pyrazoles / pharmacokinetics
-
Recombinant Proteins / antagonists & inhibitors
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Structure-Activity Relationship
Substances
-
Protein Kinase Inhibitors
-
Pyrazoles
-
Recombinant Proteins
-
Proto-Oncogene Proteins B-raf