Design and synthesis of novel substituted naphthyridines as potential c-Met kinase inhibitors based on MK-2461. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Wu, Jing-Fang; Liu, Ming-Ming; Huang, Shao-Xu; Wang, Yang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3251
• Page End: 3255
• Publication Date: 2015-08-15
• Subjects: c-Met kinase inhibitors -- MK-2461 -- 1, 5-Naphthyridine derivatives -- 1, 6-Naphthyridine derivatives -- Cytotoxic activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.082
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Two series of novel 1, 5-naphthyridine and 1, 6-naphthyridine derivatives were designed and synthesized based on the c-Met kinase inhibitor MK-2461 under the guidance of scaffold hopping strategy. All were tested on c-Met kinase and in vitro anti-tumor activities against Hela and A549 cell lines. The results indicated that 1, 6-naphthyridine was a more promising c-Met inhibitory structure core compared with 1, 5-naphthyridine. Among them, 26b and26c showed the best enzymic and cytotoxic activities. The western blot experiments implied that the cytotoxic activity of26c might be partially through suppressing the phosphorylation of c-Met kinase.