Bioorganic & Medicinal Chemistry Letters 2010-10-15

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

Chih-Hung Chen, 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

Index: Bioorg. Med. Chem. Lett. 20(20) , 6129-32, (2010)

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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.Copyright © 2010 Elsevier Ltd. All rights reserved.