基于替匹法尼骨架的苯并咪唑酮类和吲哚类化合物作为非硫醇法尼基转移酶抑制剂：合成与活性
Benzimidazolones and indoles as non-thiol farnesyltransferase inhibitors based on tipifarnib scaffold: synthesis and activity.
作者信息
Li Qun, Li Tongmei, Woods Keith W, Gu Wen-Zhen, Cohen Jerry, Stoll Vincent S, Galicia Tomas, Hutchins Charles, Frost David, Rosenberg Saul H, Sham Hing L
机构信息
Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064-6101, USA.
出版信息
Bioorg Med Chem Lett. 2005 Jun 2;15(11):2918-22. doi: 10.1016/j.bmcl.2005.03.049. Epub 2005 Apr 21.
A series of analogs of tipifarnib (1) has been synthesized as inhibitors of FTase by substituting the benzimidazolones and indoles for the 2-quinolone of tipifarnib. The novel benzimidazolones are potent and selective FTase inhibitors (FTIs) with IC(50) values of the best compounds close to that of tipifarnib. The current series demonstrate good cellular activity as measured in their inhibiting the Ras processing in NIH-3T3 cells, with compounds 2c and 2f displaying EC(50) values of 18 and 22nM, respectively.
通过用苯并咪唑酮和吲哚取代替匹法尼的2-喹诺酮，合成了一系列替匹法尼（1）类似物作为法尼基转移酶（FTase）抑制剂。新型苯并咪唑酮是强效且选择性的FTase抑制剂（FTIs），最佳化合物的IC(50)值接近替匹法尼。在抑制NIH-3T3细胞中Ras加工的实验中，当前系列显示出良好的细胞活性，化合物2c和2f的EC(50)值分别为18和22nM。
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