Design, synthesis, and structure-activity relationship of new isobenzofuranone ligands of protein kinase C

被引：31

作者：

Baba, Y

Ogoshi, Y

Hirai, G

Yanagisawa, T

Nagamatsu, K

Mayumi, S

Hashimoto, Y

Sodeoka, M

机构：

[1] Tohoku Univ, IMRAM, Sendai, Miyagi 9808577, Japan

[2] Sagami Chem Res Ctr, Kanagawa, Japan

[3] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 11期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/j.bmcl.2004.02.097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Protein kinase C (PKC) is a family of enzymes, which play important roles in intracellular signal transduction. We have designed novel PKC ligands having an isobenzofuranone template, based on the proposed interaction of DAG (1,2-diacyl-sn-glycerol) with the PKCdelta C1B ligand-binding domain. Several isobenzofuranone derivatives were synthesized and their PKCalpha binding activities were evaluated. The pivaloyl derivative 1f was found to be a strong PKCalpha ligand, and the structure-activity relationship is well explained by our proposed binding model. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2963 / 2967

页数：5

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