title: 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives: a novel type II Raf kinase inhibitors.
abstract: 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.
authors.affiliation: Life/Health Division, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Yu
authors.forename: Yunkyung
authors.initials: Y
authors.lastname: Jung
authors.forename: Hwan
authors.initials: H
authors.lastname: Kim
authors.forename: Junghun
authors.initials: J
authors.lastname: Lee
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Oh
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Yoo
authors.forename: Taebo
authors.initials: T
authors.lastname: Sim
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
mesh_terms: 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*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D048490:raf Kinases