Discovery of highly potent and selective type I B-Raf kinase inhibitors.
A series of pyrazolo[1,5-alpha]pyrimidine analogs has been prepared and found to be potent and selective B-Raf inhibitors. Molecular modeling suggests they bind to the active conformation of the enzyme.
Wang
Xiaolun
X
Chemical Sciences, Wyeth Research, Pearl River, NY 10965, USA. xxw104@gmail.com
Berger
Dan M
DM
Salaski
Edward J
EJ
Torres
Nancy
N
Hu
Yongbo
Y
Levin
Jeremy I
JI
Powell
Dennis
D
Wojciechowicz
Donald
D
Collins
Karen
K
Frommer
Eileen
E
D055808:Drug Discovery; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C527752:pyrazolo(1,5-a)pyrimidine; D048493:Proto-Oncogene Proteins B-raf