title: Design, synthesis and bioevaluation of N-trisubstituted pyrimidine derivatives as potent aurora A kinase inhibitors.
abstract: The design and synthesis of a new series of N-trisubstituted (at C2, C4 and C6 respectively) pyrimidine derivatives were reported, their in vitro structure-activity relationships vs. aurora A kinase were also discussed. Our results demonstrated that the introduction of characteristic N-substituted side chain at C2 of pyrimidines possessed a potent aurora A inhibitory activity, the position and the nature of the substituents on the phenyl ring of aniline side chain played key roles in cellular kinase inhibitory potency. Most tested compounds exhibited good inhibitory activities against aurora A kinase and various human tumor cell lines. Compounds 7j, 7m-n and 7p showed strong growth-inhibitory activities in the solid CNE-2 tumor cell and selectively blocked cell-cycle progression at the G2/M phase.
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.
authors.forename: Zi-Jie
authors.initials: ZJ
authors.lastname: Long
authors.affiliation: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, PR China.
authors.forename: Zheng-Chao
authors.initials: ZC
authors.lastname: Tu
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Ji-Quan
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China. Electronic address: liuq9@mail.sysu.edu.cn.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China; Institute of Human Virology, Sun Yat-sen University, Guangzhou 510080, PR China. Electronic address: lugui@mail.sysu.edu.cn.
authors.forename: Gui
authors.initials: G
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D064096:Aurora Kinase A; C030986:pyrimidine
keywords: Antitumor; Aurora A kinase; Pyrimidine derivative; Small molecule inhibitor; Synthesis