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
  • 1. Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan. [email protected]
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.