Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents

Yen Shih Tung, Mohane Selvaraj Coumar, Yu Shan Wu, Hui Yi Shiao, Jang-Yang Chang, Jing Ping Liou, Paritosh Shukla, Chun Wei Chang, Chi Yen Chang, Ching Chuan Kuo, Teng Kuang Yeh, Chin Yu Lin, Jian Sung Wu, Su Ying Wu, Chun Chen Liao, Hsing Pang Hsieh

研究成果: Article

56 引文 斯高帕斯(Scopus)

摘要

Utilizing scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F < 10%).

原文English
頁(從 - 到)3076-3080
頁數5
期刊Journal of Medicinal Chemistry
54
發行號8
DOIs
出版狀態Published - 2011 四月 28

    指紋

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

引用此

Tung, Y. S., Coumar, M. S., Wu, Y. S., Shiao, H. Y., Chang, J-Y., Liou, J. P., Shukla, P., Chang, C. W., Chang, C. Y., Kuo, C. C., Yeh, T. K., Lin, C. Y., Wu, J. S., Wu, S. Y., Liao, C. C., & Hsieh, H. P. (2011). Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents. Journal of Medicinal Chemistry, 54(8), 3076-3080. https://doi.org/10.1021/jm101027s