Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C

被引：160

作者：

Matsumoto, N

Ariga, A

To-e, S

Nakamura, H

Agata, N

Hirano, S

Inoue, J

Umezawa, K ^{[1
]}

机构：

[1] Keio Univ, Fac Sci & Technol, Dept Appl Chem, Kohoku Ku, Yokohama, Kanagawa 2230061, Japan

[2] Mercian Corp, Cent Res Labs, Kanagawa 2510057, Japan

[3] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1080071, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 09期

基金：

日本科学技术振兴机构;

关键词：

D O I：

10.1016/S0960-894X(00)00114-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In order to develop new inhibitors of NF-kappa B activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappa B in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：865 / 869

页数：5

共 10 条

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