Aza-stilbenes as potent and selective c-RAF inhibitors.
The synthesis of several novel aza-stilbene derivatives was carried out. The compounds were tested for their c-RAF enzyme inhibition. Compound 27 possesses significant potency against c-RAF and demonstrates selectivity over other protein kinases. A hypothesis for the binding mode, activity, and selectivity is proposed.
McDonald
Octerloney
O
GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
Lackey
Karen
K
Davis-Ward
Ronda
R
Wood
Edgar
E
Samano
Vicente
V
Maloney
Patrick
P
Deanda
Felix
F
Hunter
Robert
R
D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D004789:Enzyme Activation / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001372:Aza Compounds; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; D019908:Proto-Oncogene Proteins c-raf