Identification of pyrazolo[1,5-a]pyrimidine-3-carboxylates as B-Raf kinase inhibitors.
B-Raf kinase plays a critical role in the Raf-MEK-ERK signaling pathway and inhibitors of B-Raf could be used in the treatment of melanomas, colorectal cancer, and other Ras related human cancers. We have identified novel small molecule pyrazolo[1,5-a]pyrimidine derivatives as B-Raf kinase inhibitors. Structure-activity relationship was generated for various regions of the scaffold to improve the biochemical profile.
Gopalsamy
Ariamala
A
Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. gopalsa@wyeth.com
Ciszewski
Greg
G
Hu
Yongbo
Y
Lee
Frederick
F
Feldberg
Larry
L
Frommer
Eileen
E
Kim
Steven
S
Collins
Karen
K
Wojciechowicz
Donald
D
Mallon
Robert
R
D045744:Cell Line, Tumor; D003198:Computer Simulation; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D048493:Proto-Oncogene Proteins B-raf