1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives: a novel type II Raf kinase inhibitors.
The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC(50)=0.56-0.86 microM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.
Yu
Hana
H
Life/Health Division, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Jung
Yunkyung
Y
Kim
Hwan
H
Lee
Junghun
J
Oh
Chang-Hyun
CH
Yoo
Kyung Ho
KH
Sim
Taebo
T
Hah
Jung-Mi
JM
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D048490:raf Kinases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D048490:raf Kinases