New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity

被引：74

作者：

Lankau, Hans-Joachim ^{[1
]}

Unverferth, Klaus ^{[1
]}

Grunwald, Christian ^{[1
]}

Hartenhauer, Helge ^{[1
]}

Heinecke, Kristina ^{[1
]}

Bernoester, Katrin ^{[1
]}

Dost, Rita ^{[1
]}

Egerland, Ute ^{[1
]}

Rundfeldt, Chris ^{[1
]}

机构：

[1] Elbion AG, Dept Med Chem, D-01445 Radebuel, Saxony, Germany

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 42卷 / 06期

关键词：

1,2,4-oxadiazole derivatives; synthesis; pentylenetetrazole test; maximal electroshock seizure test; anticonvulsant activity;

D O I：

10.1016/j.ejmech.2006.12.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 3- and 5-aryl-1,2,4-oxadiazole derivatives were prepared and tested for anticonvulsant activity in a variety of models. These 1,2,4oxadiazoles exhibit considerable activity in both pentylenetetrazole (PTZ) and maximal electroshock seizure (MES) models. Compound 10 was protective in the PTZ model in rats with an oral ED50 of 25.5 mg/kg and in the MES model in rats with an oral ED50 Of 14.6 mg/kg. Neurotoxicity (rotarod) was observed with an ED50 Of 335 mg/kg. We found several oxadiazoles that acted as selective GABA potentiating compounds with no interaction to the benzodiazepine binding site. (c) 2007 Elsevier Masson SAS. All rights reserved.

引用

页码：873 / 879

页数：7

共 50 条

[31] Synthesis and anticancer activity of 3,5-diaryl-1,2,4-oxadiazole derivatives
Kundu, Mrityunjoy
Singh, Jagadish
Singh, Brijesh
Ghosh, Tirtha
Maiti, B. C.
Maity, T. K.
INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, 2012, 51 (03): : 493 - 497
[32] NEW 1,2,4-OXADIAZOLE DERIVATIVES - SYNTHESIS AND ADRENERGIC-RECEPTORS BINDING-STUDIES
BRIZZI, V
BRUFANI, M
FILOCAMO, L
BRUNI, G
FIASCHI, AI
FARMACO, 1992, 47 (06): : 953 - 966
[33] 3-AMINO-1,2,4-OXADIAZOLE AND 3-CYANO-1,2,4-OXADIAZOLE
GREGORY, GI
SEALE, PW
WARBURTO.WK
WILSON, MJ
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1973, (01): : 47 - 51
[34] SYNTHESIS AND CHARACTERIZATION OF NEW THIAZOLYL 1,3,4-OXADIAZOLE AND 1,2,4-TRIAZOLE DERIVATIVES
Darekar, Nirmala R.
Dengale, Sujata G.
Sasane, Kulbhushan A.
Patil, Shripad M.
Akolkar, Hemantkumar N.
HETEROCYCLIC LETTERS, 2024, 14 (02):
[35] HETEROCYCLIC TRANSFORMATIONS BY HYDROGENOLYSIS - PYRIMIDINE-DERIVATIVES FROM 1,2,4-OXADIAZOLE DERIVATIVES
RUCCIA, M
VIVONA, N
CUSMANO, G
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1974, 11 (05) : 829 - 830
[36] Design, Synthesis and Anti-fungal Activity of 1,2,4-Oxadiazole Derivatives Containing Diamide Moiety
Wang Feng
Chen Yu
Pei Hongyan
Liu Dongdong
Luo Chunfeng
Zhang Jing
Zhang Lixin
CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE, 2023, 44 (11):
[37] Exploration of the structure-activity relationship of 1,2,4-oxadiazole antibiotics
Ding, Derong
Boudreau, Marc A.
Leemans, Erika
Spink, Edward
Yamaguchi, Takao
Testero, Sebastian A.
O'Daniel, Peter I.
Lastochkin, Elena
Chang, Mayland
Mobashery, Shahriar
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (21) : 4854 - 4857
[38] Design, Synthesis, Nematicidal Activity, and Mechanism of Novel Amide Derivatives Containing an 1,2,4-Oxadiazole Moiety
Wang, Yu
Song, Hongyi
Wang, Sheng
Cai, Qingfeng
Chen, Jixiang
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2023, 72 (01) : 128 - 139
[39] Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments
Liu, Dan
Luo, Ling
Wang, Zhengxing
Ma, Xiaoyun
Gan, Xiuhai
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (03)
[40] Electrocyclic Ring-Opening of 1,2,4-Oxadiazole[4,5-a]piridinium Chloride: a New Route to 1,2,4-Oxadiazole Dienamino Compounds
Carella, Stefano
Memeo, Misal Giuseppe
Quadrelli, Paolo
CHEMISTRYOPEN, 2019, 8 (09): : 1209 - 1221

← 1 2 3 4 5 →