title: Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors.
abstract: The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50=38.3 nM and 8.79 nM).
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Junghun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Hyangmi
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
authors.forename: Waqar
authors.initials: W
authors.lastname: Aman
authors.affiliation: College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
authors.forename: Jae-Sang
authors.initials: JS
authors.lastname: Ryu
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea. Electronic address: jhah@hanyang.ac.kr.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D048493:Proto-Oncogene Proteins B-raf
keywords: (4-Aminobenzyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives; Antiproliferative activity; BRAF V600E; CRAF; Melanoma; Selectivity