1433784-87-2Relevant academic research and scientific papers
Three substituted naphthyridine compounds and its preparation and use
-
Paragraph 0123; 0125, (2017/04/14)
The invention relates to 1,3,5-tri-substituted-1H-imidazo[4,5-h]1,6-diazanaphthalene-2(3H)-one compounds shown as the general formula I, isomers thereof and pharmaceutically acceptable salts thereof, a preparation method and applications thereof, and comp
Investigation on the 1,6-naphthyridine motif: Discovery and SAR study of 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one-based c-Met kinase inhibitors
Wang, Yong,Xu, Zhong-Liang,Ai, Jing,Peng, Xia,Lin, Jian-Ping,Ji, Yin-Chun,Geng, Mei-Yu,Long, Ya-Qiu
, p. 1545 - 1562 (2013/05/09)
The 1,6-naphthyridine motif is a multivalent scaffold in medicinal chemistry presenting various bioactivities when properly substituted. By incorporating a cyclic urea pharmacophore into the 1,6-naphthyridine framework through conformationally constraining the 7,8-positions, the resulting 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one was identified as a new class of c-Met kinase inhibitor. A comprehensive SAR study indicated that an N-1 alkyl substituent bearing a terminal free amino group, a hydrophobic substituted benzyl group at the N-3 position and the tricyclic core were essential for retaining effective Met inhibition of the 1H-imidazo[4,5-h][1,6]naphthyridin- 2(3H)-one chemotype. Further introduction of a 4′-carboxamide phenoxy group at the C-5 position significantly improved the potency. The best c-Met kinase inhibitory activity was exemplified by 2t with an IC50 = 2.6 μM, which also displayed effective inhibition against TPR-Met phosphorylation and the proliferation of the BaF3-TPR-Met cells at low micromolar concentrations.
