title: Design, Synthesis, and Biological Evaluation of Substituted Pyrimidines as Potential Phosphatidylinositol 3-Kinase (PI3K) Inhibitors.
abstract: Three series of substituted pyrimidines were designed and synthesized. All target compounds were screened for kinase inhibitory activities against PI3Kα, and most IC50 values were found within the nanomolar range. Compounds 5d and 5p displayed comparable activities relative to the positive control 5a. 5p also showed a significant isozyme selectivity (PI3Kβ/α). Furthermore, the cytotoxicities of these pyrimidines against human cancer cell lines were evaluated and the in vivo anticancer effect of 5d was also tested.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.|College of Pharmacy, Guizhou Medical University , Guiyang, 550004, PR China.
authors.forename: Ji-Quan
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Luo
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.
authors.forename: Yan-Shi
authors.initials: YS
authors.lastname: Xiong
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
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: Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University , Guangzhou, 510260, PR China.
authors.forename: Zi-Jie
authors.initials: ZJ
authors.lastname: Long
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University , Guangzhou, 510060, PR China.
authors.forename: Xiao-Ju
authors.initials: XJ
authors.lastname: Lai
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.
authors.forename: Hui-Xuan
authors.initials: HX
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Chemistry, 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 Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Weng
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, 510006, PR China.|Institute of Human Virology, Sun Yat-sen University , Guangzhou, 510080, PR China.
authors.forename: Gui
authors.initials: G
authors.lastname: Lu
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; D015394:Molecular Structure; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D058539:Phosphatidylinositol 3-Kinase