Structure-based design of isoindoline-1,3-diones and 2,3-dihydrophthalazine-1,4-diones as novel B-Raf inhibitors.
Structure-guided design led to the discovery of novel chemical scaffolds for B-Raf inhibitors. Both type I and type II kinase inhibitors have been explored and lead compounds with good potency and excellent selectivity have been identified.
Pfizer Worldwide Research and Development, Pearl River, NY 10965, USA. xxw104@gmail.com
Xiaolun
X
Wang
Edward J
EJ
Salaski
Dan M
DM
Berger
Dennis
D
Powell
Yongbo
Y
Hu
Donald
D
Wojciechowicz
Karen
K
Collins
Eileen
E
Frommer
D001557:Benzenesulfonates / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D000077157:Sorafenib; D013329:Structure-Activity Relationship
D001557:Benzenesulfonates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D054833:Isoindoles; D010671:Phenylurea Compounds; D010793:Phthalazines; D011725:Pyridines; C508204:SB-590885; D009536:Niacinamide; D000077157:Sorafenib; D048493:Proto-Oncogene Proteins B-raf