Computer-Guided Design, Synthesis, and Protein Kinase C Affinity of a New. Salicylate-Based Class of Bryostatin Analogs

被引:28
|
作者
Wender, Paul A. [1 ]
Nakagawa, Yu
Near, Katherine E.
Staveness, Daryl
机构
[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
PHORBOL ESTER PHARMACOPHORE; STRUCTURAL BASIS; ACTIVATION; PKC; AGENTS; ALPHA; STEP;
D O I
10.1021/ol502491f
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Bryostatin 1 is in clinical trials for the treatment of cancer and alzheimer disease and is a candidate for a first in class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a funciton oriented synthesis strategy, a new class of bryostatin inspired analog was designed with a simplified salicylate-derived subunit, enabling step economical synthesis (23 total steps) of agents exhibiting bryostatin like affinity to protein kinase C (PKC).
引用
收藏
页码:5136 / 5139
页数:4
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