title: Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors.
abstract: A series of azulene-based derivatives were synthesized as potent inhibitors for receptor tyrosine kinases such as FMS-like tyrosine kinase 3 (FLT-3). Systematic side chain modification of prototype 1a was carried out through SAR studies. Analogue 22 was identified from this series and found to be one of the most potent FLT-3 inhibitors, with good pharmaceutical properties, superior efficacy, and tolerability in a tumor xenograft model.
authors.affiliation: Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan. ChihHungChen@itri.org.tw
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: On
authors.initials: O
authors.lastname: Lee
authors.forename: Chung-Niang
authors.initials: CN
authors.lastname: Yao
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Chuang
authors.forename: Yow-Lone
authors.initials: YL
authors.lastname: Chang
authors.forename: May-Hua
authors.initials: MH
authors.lastname: Chang
authors.forename: Yen-Fang
authors.initials: YF
authors.lastname: Wen
authors.forename: Wan-Hsu
authors.initials: WH
authors.lastname: Yang
authors.forename: Ching-Huai
authors.initials: CH
authors.lastname: Ko
authors.forename: Nien-Tzu
authors.initials: NT
authors.lastname: Chou
authors.forename: Mai-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Chin-Pen
authors.initials: CP
authors.lastname: Lai
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Sun
authors.forename: Ling-mei
authors.initials: LM
authors.lastname: Wang
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Tzong-Hsiung
authors.initials: TH
authors.lastname: Hseu
authors.forename: Chia-Ni
authors.initials: CN
authors.lastname: Chang
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Hsu
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Lin
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Chang
authors.forename: Ying-Chu
authors.initials: YC
authors.lastname: Shih
authors.forename: Shuen-Hsiang
authors.initials: SH
authors.lastname: Chou
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: Hsiang-Wen
authors.initials: HW
authors.lastname: Tseng
authors.forename: Chih-Peng
authors.initials: CP
authors.lastname: Liu
authors.forename: Chia-Mu
authors.initials: CM
authors.lastname: Tu
authors.forename: Tsan-Lin
authors.initials: TL
authors.lastname: Hu
authors.forename: Yuan-Jang
authors.initials: YJ
authors.lastname: Tsai
authors.forename: Ting-Shou
authors.initials: TS
authors.lastname: Chen
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: Shu-Jiau
authors.initials: SJ
authors.lastname: Chiou
authors.forename: Chung-Cheng
authors.initials: CC
authors.lastname: Liu
authors.forename: Chrong-Shiong
authors.initials: CS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D052176:Azulenes / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D052176:Azulenes; C005525:azulene; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3