title: Scaffold-hopping strategy: synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents.
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%).
authors: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan, ROC.
authors: Yen-Shih
authors: YS
authors: Tung
authors: Mohane Selvaraj
authors: MS
authors: Coumar
authors: Yu-Shan
authors: YS
authors: Wu
authors: Hui-Yi
authors: HY
authors: Shiao
authors: Jang-Yang
authors: JY
authors: Chang
authors: Jing-Ping
authors: JP
authors: Liou
authors: Paritosh
authors: P
authors: Shukla
authors: Chun-Wei
authors: CW
authors: Chang
authors: Chi-Yen
authors: CY
authors: Chang
authors: Ching-Chuan
authors: CC
authors: Kuo
authors: Teng-Kuang
authors: TK
authors: Yeh
authors: Chin-Yu
authors: CY
authors: Lin
authors: Jian-Sung
authors: JS
authors: Wu
authors: Su-Ying
authors: SY
authors: Wu
authors: Chun-Chen
authors: CC
authors: Liao
authors: Hsing-Pang
authors: HP
authors: Hsieh
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D001682:Biological Availability; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds