Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines.
The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC(50)=0.62 and 4.49muM, respectively) and turned out to be a selective and potent CRAF inhibitor.
Life/Health Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Junghun
J
Lee
Hwan
H
Kim
Hana
H
Yu
Jae Yoon
JY
Chung
Chang-Hyun
CH
Oh
Kyung Ho
KH
Yoo
Taebo
T
Sim
Jung-Mi
JM
Hah
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000737:chemistry / Q000627:therapeutic use; D001665:Binding Sites; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000627:therapeutic use; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000077157:Sorafenib; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007093:Imidazoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D009536:Niacinamide; D000077157:Sorafenib; D011494:Protein Kinases; D019908:Proto-Oncogene Proteins c-raf; C030986:pyrimidine