Development of new fluorescent xanthines as kinase inhibitors.
An efficient and versatile synthetic approach for the preparation of highly substituted xanthine derivatives has been developed by a combination of direct N7- and C8-arylation. With this method, diverse xanthine analogues were prepared and potent kinase inhibitors could be identified. For example, compound 8a inhibits PI3Ks and proliferation in T47D tumor cells. In addition, these xanthine-based kinase inhibitors exhibited significant fluorescence emission in a concentration-dependent response.
Kim
Donghee
D
Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
Jun
Hwiseok
H
Lee
Hyunseung
H
Hong
Soon-Sun
SS
Hong
Sungwoo
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D047428:Protein Kinase Inhibitors; D014970:Xanthines; D011494:Protein Kinases