Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment

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• 作者：Lori M. Miller ; Scott C. Mayer ; Dan M. Berger ; Diane H. Boschelli ; Frank Boschelli ; Li Di ; Xuemei Du ; Minu Dutia ; Middleton B. Floyd ; Mark Johnson ; Cynthia Hess Kenny ; Girija Krishnamurthy ; Franklin M
• 关键词：IGFR inhibitor ; Cyanoquinoline ; ‘ ; Hit to Lead’ ; investigations
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 January 2009
• 年：2009
• 卷：19
• 期：1
• 页码：62-66
• 全文大小：196 K

文摘

Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.