S-法尼基硫代丙酸（FTPA）三唑类化合物作为异戊二烯基半胱氨酸羧基甲基转移酶的强效抑制剂
S-Farnesyl-Thiopropionic Acid (FTPA) Triazoles as Potent Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase.
作者信息
Bergman Joel A, Hahne Kalub, Song Jiao, Hrycyna Christine A, Gibbs Richard A
机构信息
Department of Medicinal Chemistry and Molecular Pharmacology and the Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
出版信息
ACS Med Chem Lett. 2012 Jan 12;3(1):15-19. doi: 10.1021/ml200106d. Epub 2011 Nov 28.
Abstract
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 analog is a potent inhibitor of Icmt (IC(50) = 0.8 ± 0.1 μM; calculated K(i) = 0.4 μM).
摘要
我们报告了新型FTFA-三唑化合物的设计与合成，该化合物是异戊烯基半胱氨酸羧基甲基转移酶（Icmt）的有效抑制剂，重点关注硫醚和类异戊二烯模拟物。利用铜辅助环加成反应将这些模拟物偶联，以组装潜在的抑制剂。将偶联反应生成的三唑用作异戊烯基模拟物，得到了联苯取代的FTFA三唑10n。这种脂质修饰的类似物是Icmt的有效抑制剂（IC(50) = 0.8 ± 0.1 μM；计算得出的K(i) = 0.4 μM）。
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