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

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Abstract

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%).

Original languageEnglish
Pages (from-to)3076-3080
Number of pages5
JournalJournal of Medicinal Chemistry
Volume54
Issue number8
DOIs
Publication statusPublished - Apr 28 2011

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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