Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents
Journal of Medicinal Chemistry2011Vol. 54(8), pp. 3076–3080
Citations Over TimeTop 12% of 2011 papers
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
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%).
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