2. Academic Validation
  3. Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors

Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors

  • Bioorg Med Chem Lett. 2010 Oct 15;20(20):6129-32. doi: 10.1016/j.bmcl.2010.08.025.
Chih-Hung Chen 1,  On Lee,  Chung-Niang Yao,  Meng-Yun Chuang,  Yow-Lone Chang,  May-Hua Chang,  Yen-Fang Wen,  Wan-Hsu Yang,  Ching-Huai Ko,  Nien-Tzu Chou,  Mai-Wei Lin,  Chin-Pen Lai,  Chung-Yuan Sun,  Ling-mei Wang,  Yen-Chun Chen,  Tzong-Hsiung Hseu,  Chia-Ni Chang,  Hui-Chun Hsu,  Hui-Chi Lin,  Yu-Li Chang,  Ying-Chu Shih,  Shuen-Hsiang Chou,  Yi-Ling Hsu,  Hsiang-Wen Tseng,  Chih-Peng Liu,  Chia-Mu Tu,  Tsan-Lin Hu,  Yuan-Jang Tsai,  Ting-Shou Chen,  Chih-Lung Lin,  Shu-Jiau Chiou,  Chung-Cheng Liu,  Chrong-Shiong Hwang
Affiliations

Affiliation

  • 1 Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan. ChihHungChen@itri.org.tw
PMID: 20833039 DOI: 10.1016/j.bmcl.2010.08.025
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.

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