Li Qun, Wang Gary T, Li Tongmei, Gwaltney Stephen L, Woods Keith W, Claiborne Akiyo, Wang Xilu, Gu Wendy, Cohen Jerry, Stoll Vincent S, Hutchins Charles, Frost David, Rosenberg Saul H, Sham Hing L
Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064-6101, USA.
Bioorg Med Chem Lett. 2004 Nov 1;14(21):5371-6. doi: 10.1016/j.bmcl.2004.08.011.
A series of imidazole-containing methyl ethers (4-5) have been designed and synthesized as potent and selective farnesyltransferase inhibitors (FTIs) by transposition of the D-ring to the methyl group on the imidazole of the previously reported FTIs 3. Several compounds such as 4h and 5b demonstrate superior enzymatic activity to the current benchmark compound tipifarnib (1) with IC(50) values in the lower subnanomolar range, while maintaining excellent cellular activity comparable to tipifarnib. The compounds are characterized as being simple, easier to make, and possess no chiral center involved.
通过将D环转位至先前报道的法尼基转移酶抑制剂(FTIs)3的咪唑甲基上,设计并合成了一系列含咪唑的甲基醚(4-5)作为强效且选择性的法尼基转移酶抑制剂。几种化合物如4h和5b表现出优于当前基准化合物替匹法尼(1)的酶活性,IC50值处于低亚纳摩尔范围,同时保持与替匹法尼相当的优异细胞活性。这些化合物的特点是结构简单、易于制备且不涉及手性中心。