Synthesis and anticonvulsant activity of N-(2-hydroxyethyl) cinnamamide derivatives

被引：43

作者：

Guan, Li-Ping ^{[1
,2
]}

Wei, Cheng-Xi ^{[1
]}

Deng, Xian-Qing ^{[1
]}

Sui, Xin ^{[1
]}

Piao, Hu-Ri ^{[1
]}

Quan, Zhe-Shan ^{[1
,2
]}

机构：

[1] Yanbian Univ, Coll Pharm, Yanji 133000, Jilin, Peoples R China

[2] Yanbian Univ, Minist Educ, Key Lab Organism Funct Factors Changbai Mt, Yanji 133002, Jilin, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 09期

基金：

中国国家自然科学基金;

关键词：

Cinnamamide derivatives; Maximal electroshock (MES); Chemical induced models; Neurotoxicity; GABA; SYSTEM; DRUGS;

D O I：

10.1016/j.ejmech.2009.02.015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel N-(2-hydroxyethyl) cinnamamide derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The MES test showed that compounds l(N-(2-hydroxyethyl) cinnamamide) and 1d ((E)-3-(3-fluorophenyl)-N-(2-hydroxyethyl)acrylamide) were found to possess better anticonvulsant activity but also had lower toxicity. In the anti-MES potency test, these compounds exhibited median effective dose (ED50) of 17.7 and 17.0 mg/kg, respectively, and median toxicity dose (TD50) of 154.9 and 211.1, respectively, resulting in a protective index (PI) of 8.8 and 12.4, respectively, which is much greater than the PI of the marked antiepileptic drug carbamazepine. To further investigate the effects of the anticonvulsant activity in several different models, compounds I and 1d were tested against convulsions induced by chemical substances, including pentylenetetrazole (PTZ), isoniazid, 3-mercaptopropionic acid, and thiosemicarbazide. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：3654 / 3657

页数：4

共 50 条

[1] Synthesis and Anticonvulsant Activity of N-(2-Hydroxyethyl)amide Derivatives
Guan, Li-Ping
Zhao, Dong-Hai
Xiu, Jing-Hui
Sui, Xin
Piao, Hu-Ri
Quan, Zhe-Shan
[J]. ARCHIV DER PHARMAZIE, 2009, 342 (01) : 34 - 40
[2] Synthesis and antidepressant-like action of N-(2-hydroxyethyl) cinnamamide derivatives in mice
Deng, Xian-Qing
Wu, Di
Wei, Cheng-Xi
Quan, Zhe-Shan
[J]. MEDICINAL CHEMISTRY RESEARCH, 2011, 20 (08) : 1273 - 1279
[3] Synthesis and antidepressant-like action of N-(2-hydroxyethyl) cinnamamide derivatives in mice
Xian-Qing Deng
Di Wu
Cheng-Xi Wei
Zhe-Shan Quan
[J]. Medicinal Chemistry Research, 2011, 20 : 1273 - 1279
[4] Synthesis and biological activity of N-(2-hydroxyethyl)cytisine derivatives
D. V. Shishkin
A. R. Shaimuratova
A. N. Lobov
N. Z. Baibulatova
L. V. Spirikhin
M. S. Yunusov
N. S. Makara
N. Zh. Baschenko
V. A. Dokichev
[J]. Chemistry of Natural Compounds, 2007, 43 : 190 - 196
[5] Synthesis and biological activity of N-(2-hydroxyethyl)cytisine derivatives
Shishkin, D. V.
Shaimuratova, A. R.
Lobov, A. N.
Baibulatova, N. Z.
Spirikhin, L. V.
Yunusov, M. S.
Makara, N. S.
Baschenko, N. Zh.
Dokichev, V. A.
[J]. CHEMISTRY OF NATURAL COMPOUNDS, 2007, 43 (02) : 190 - 196
[6] Synthesis of N-(2-hydroxyethyl) derivatives of β-alanine
T. V. Dokichev
D. R. Latypova
R. Z. Biglova
R. F. Talipov
[J]. Doklady Chemistry, 2010, 430 : 47 - 49
[7] Synthesis of N-(2-hydroxyethyl) derivatives of β-alanine
Dokichev, T. V.
Latypova, D. R.
Biglova, R. Z.
Talipov, R. F.
[J]. DOKLADY CHEMISTRY, 2010, 430 : 47 - 49
[8] Synthesis of N-(2-hydroxyethyl)piperidines and N-(2-hydroxyethyl)perhydroquinolines
N. G. Chernyshevskii Saratov State University, 410601 Saratov, Russia
[J]. Chem. Heterocycl. Compd., 6 (745-746):
[9] Synthesis of N-(2-Hydroxyethyl)piperidines and N-(2-Hydroxyethyl)perhydroquinolines
Golikov, A. G.
Reshetov, P. V.
Kriven'ko, A. P.
[J]. Chemistry of Heterocyclic Compounds, 33 (06):
[10] Synthesis of N-(2-hydroxyethyl)piperidines and N-(2-hydroxyethyl)perhydroquinolines
Golikov A.G.
Reshetov P.V.
Kriven'ko A.P.
[J]. Chemistry of Heterocyclic Compounds, 1997, 33 (6) : 745 - 746

← 1 2 3 4 5 →