3-取代-2-氧代-1,4-噻嗪的合成及其对小鼠内毒素休克保护作用的评价。

Synthesis of 3-substituted 2-oxo-1,4-thiazines and evaluation of their protective effect against endotoxin shock in mouse.

作者信息

Yamazaki H, Harada H, Matsuzaki K, Watanabe T, Saito H

机构信息

Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1992 Apr;40(4):1025-8. doi: 10.1248/cpb.40.1025.

DOI:10.1248/cpb.40.1025

PMID:1525932

Abstract

5-Methyl-2,3-dioxo-2H,4H-1,4-thiazine (7) was obtained by the oxidation of 5-methyl-2H-1,4-thiazin-3(4H)-one (5) with m-chloroperbenzoic acid in MeOH, followed by acid hydrolysis of the resulting 2,2-dimethoxy-1,4-thiazine (6). 3-Chloro-2-oxo-1,4-thiazine (10), which was obtained from 7 by heating with phosphorous oxychloride, reacted with various nucleophiles to give 3-substituted 2-oxo-1,4-thiazines (11a--y). Some of these 2-oxo-1,4-thiazines, 11a--b, e, o and r--s, showed a protective effect against endotoxin shock in D-galactosamine-sensitized mice.

摘要

5-甲基-2,3-二氧代-2H,4H-1,4-噻嗪（7）是通过在甲醇中用间氯过苯甲酸氧化5-甲基-2H-1,4-噻嗪-3(4H)-酮（5），然后对所得的2,2-二甲氧基-1,4-噻嗪（6）进行酸水解而制得的。由7与三氯氧磷加热反应得到的3-氯-2-氧代-1,4-噻嗪（10）与各种亲核试剂反应，生成3-取代的2-氧代-1,4-噻嗪（11a - y）。其中一些2-氧代-1,4-噻嗪，即11a - b、e、o和r - s，在D-半乳糖胺致敏的小鼠中对内毒素休克显示出保护作用。