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

doi:10.1021/jm101027s

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

Research output: Contribution to journal › Article › peer-review

91 Citations (Scopus)

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 language	English
Pages (from-to)	3076-3080
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	54
Issue number	8
DOIs	https://doi.org/10.1021/jm101027s
Publication status	Published - Apr 28 2011

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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

Tung, YS, Coumar, MS, Wu, YS, Shiao, HY, Chang, JY , Liou, JP, Shukla, P, Chang, CW, Chang, CY, Kuo, CC, Yeh, TK, Lin, CY, Wu, JS, Wu, SY, Liao, CC & Hsieh, HP 2011, 'Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents', Journal of Medicinal Chemistry, vol. 54, no. 8, pp. 3076-3080. https://doi.org/10.1021/jm101027s

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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%).",

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

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AU - Wu, Yu Shan

AU - Shiao, Hui Yi

AU - Chang, Jang Yang

AU - Liou, Jing Ping

AU - Shukla, Paritosh

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AU - Kuo, Ching Chuan

AU - Yeh, Teng Kuang

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AU - Liao, Chun Chen

AU - Hsieh, Hsing Pang

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

Abstract

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