title: Novel 2,4-dianilino-5-fluoropyrimidine derivatives possessing ALK inhibitory activities.
abstract: A new series of 2,4-dianilino-5-fluoropyrimidine derivatives were designed and synthesized and their anaplastic lymphoma kinase (ALK) inhibitory activities were evaluated by biochemical and cell-based assays in order to discover a new ALK inhibitor. Most compounds synthesized showed good inhibitory activities against ALK and good cytotoxic activities in H3122 cell line. The best compound 6f showed good activity against wild-type ALK along with crizotinib-resistant mutant ALK, and it showed 6 times better activity in cell-based assay than crizotinib. Some SAR studies were performed by the comparisons of the activities between 6 and the designed-synthesized compounds.
authors.affiliation: Korea Research Institute of Chemical Technology, 141 Gajeongro, Yuseong, Daejeon, 305-600, Korea.
authors.forename: Jeong In
authors.initials: JI
authors.lastname: Yun
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Yang
authors.forename: Muhammad
authors.initials: M
authors.lastname: Latif
authors.forename: Hyeon Ji
authors.initials: HJ
authors.lastname: Lee
authors.forename: Kwangho
authors.initials: K
authors.lastname: Lee
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Yun
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Park
authors.forename: Chong Ock
authors.initials: CO
authors.lastname: Lee
authors.forename: Chong Hak
authors.initials: CH
authors.lastname: Chae
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Jung
authors.forename: Pilho
authors.initials: P
authors.lastname: Kim
authors.forename: Sang Un
authors.initials: SU
authors.lastname: Choi
authors.forename: Hyoung Rae
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002460:Cell Line; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C029269:5-fluoropyrimidine; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases