Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents
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- 作者：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
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：April 28, 2011
- 年：2011
- 卷：54
- 期：8
- 页码：3076-3080
- 全文大小：827K
- 年卷期：v.54,no.8(April 28, 2011)
- ISSN：1520-4804
文摘
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%).