S-Farnesyl-Thiopropionic Acid Triazoles as Potent Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase

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• 作者：Joel A. Bergman ; Kalub Hahne ; Jiao Song ; Christine A. Hrycyna ; Richard A. Gibbs
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：January 12, 2012
• 年：2012
• 卷：3
• 期：1
• 页码：15-19
• 全文大小：283K
• 年卷期：v.3,no.1(January 12, 2012)
• ISSN：1948-5875

文摘

We report the design and synthesis of novel FTPA-triazole compounds as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt), through a focus on thioether and isoprenoid mimetics. These mimetics were coupled utilizing a copper-assisted cycloaddition to assemble the potential inhibitors. Using the resulting triazole from the coupling as an isoprenyl mimetic resulted in the biphenyl-substituted FTPA triazole 10n. This lipid-modified analogue is a potent inhibitor of Icmt (IC₅₀ = 0.8 卤 0.1 渭M; calculated K_i = 0.4 渭M).

Keywords:

Isoprenylcysteine carboxyl methyltransferase (Icmt); Ras; prenylcysteine; dipolar cycloaddition; S-farnesyl-thiopropionic acid (FTPA); triazole