Design and synthesis of 7-alkoxy-4-heteroarylamino-3-quinolinecarbonitriles as dual inhibitors of c-Src kinase and nitric oxide synthase

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• 作者：Xin Cao ; Qi-Dong You ; Zhi-Yu Li ; Qing-Long Guo ; Jing Shang ; Ming Yan ; Ji-Wang Chern ; Men-Ling Chen
• 关键词：Src ; iNOS ; Dual inhibitors ; Anticancer
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：1 June 2008
• 年：2008
• 卷：16
• 期：11
• 页码：5890-5898
• 全文大小：236 K

文摘

Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC₅₀ values of 6.58 and 7.61 μM toward colon cancer HT-29 and liver cancer HepG2 cell lines.