Design and Synthesis of Imidazopyridine Analogues as Inhibitors of Phosphoinositide 3-Kinase Signaling and Angiogenesis

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• 作者：Okseon Kim ; Yujeong Jeong ; Hyunseung Lee ; Sun-Sun Hong ; Sungwoo Hong
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：April 14, 2011
• 年：2011
• 卷：54
• 期：7
• 页码：2455-2466
• 全文大小：1154K
• 年卷期：v.54,no.7(April 14, 2011)
• ISSN：1520-4804

文摘

Phosphatidylinositol 3-kinase 伪 (PI3K伪) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3K伪 can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives as PI3K伪 inhibitors through the fragment-growing strategy. By varying groups at the 3- and 6-positions of imidazo[1,2-a]pyridines, we studied the structure鈭抋ctivity relationships (SAR) profiles and identified a series of potent PI3K伪 inhibitors. Representative derivatives showed good activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.