Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

被引：24
|
作者：
Duerfeldt, Adam S. [1 ]
Brandt, Gary E. L. [1 ]
Blagg, Brian S. J. [1 ]
机构：
[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA
来源：
ORGANIC LETTERS | 2009年 / 11卷 / 11期
关键词：
MOLECULAR CHAPERONES; CHIMERIC INHIBITORS; TUMOR SELECTIVITY; BINDING-SITE; GELDANAMYCIN; PROTEIN; RADICICOL; TARGET; CANCER; EXPLANATION;
D O I：
10.1021/ol900783m
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Conformationally constrained cis-amide chimeric inhibitors of Hsp90 have been synthesized and evaluated for their Hsp90 inhibitory activity. These new compounds exhibited Hsp90 ATPase inhibition and induced Hsp90-dependent client protein degradation in a dose-dependent manner. Biological data reported herein suggests that amide bond isomerization of geldanamycin derivatives plays an important role in affinity for the heteroprotein complex present in cancer cells.
引用
收藏
页码：2353 / 2356
页数：4
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