Discovery of novel pyrrolo[2, 3-b]pyridine derivatives bearing 1, 2, 3-triazole moiety as c-Met kinase inhibitors. Issue 7 (1st April 2016)

• Record Type: Journal Article
• Authors: Tang, Qidong; Wang, Linxiao; Tu, Yayi; Zhu, Wufu; Luo, Rong; Tu, Qidong; Wang, Ping; Wu, Chunjiang; Gong, Ping; Zheng, Pengwu
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 7(2016)
• Page Start: 1680
• Page End: 1684
• Publication Date: 2016-04-01
• Subjects: Synthesis -- Pyrrolo[2, 3-b]pyridine derivatives -- 1, 2, 3-Triazole -- c-Met -- Antiproliferative activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.02.059
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: A series of pyrrolo[2, 3-b]pyridine derivatives bearing 1, 2, 3-triazole moiety (18 –45 ) were designed, synthesized and evaluated for their activity against c-Met kinase and cancer cell lines. The most promising compound34 showed excellent in vitro activity. Abstract: A series of novel pyrrolo[2, 3-b]pyridine derivatives bearing 1, 2, 3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog34 showing a c-Met IC50 value of 1.68 nM. Structure–activity relationship studies indicated that electron-withdrawing groups (X = CF3, R 1 = F, R 2 = 4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.