Synthesis and anticonvulsant activity of novel and potent 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-ones

被引：31
作者：
Grasso, S
De Sarro, G
De Sarro, A
Micale, N
Polimeni, S
Zappalà, M
Puia, G
Baraldi, M
De Micheli, C
机构：
[1] Univ Messina, Dipartimento Farmacochim, I-98168 Messina, Italy
[2] Univ Catanzaro, Dipartimento Med Sperimentale & Clin, I-88100 Catanzaro, Italy
[3] Univ Messina, Policlin Univ, Ist Farmacol, I-98100 Messina, Italy
[4] Univ Modena, Dipartimento Sci Farmaceut, I-41100 Modena, Italy
[5] Univ Milan, Ist Chim Farmaceut, I-20121 Milan, Italy
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 04期
关键词：
D O I：
10.1016/S0960-894X(00)00693-4
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The synthesis and anticonvulsant activity of 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-(thi)ones (4a-d) and their 3-N-alkylcarbamoyl derivatives (4e-h) are reported. The new compounds possess marked anticonvulsant properties, comparable to those of the dehydro analogues 3 and higher than that of GYKI 52466 (1). Noteworthy, compound 4c shows a longer-lasting anticonvulsant activity. Electrophysiological experiments show that derivative 4c is less effective than 1 and 3c to reduce the KA-evoked currents in cerebellar granule neurons. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：463 / 466
页数：4
相关论文
共 23 条
[1]   Synthesis and anticonvulsant activity of 3-aryl-5H-2,3-benzodiazepine AMPA antagonists [J].
Anderson, BA ;
Harn, NK ;
Hansen, MM ;
Harkness, AR ;
Lodge, D ;
Leander, JD .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (14) :1953-1956
[2]   THE ANTICONVULSANT EFFECT OF THE NON-NMDA ANTAGONISTS, NBQX AND GYKI-52466, IN MICE [J].
CHAPMAN, AG ;
SMITH, SE ;
MELDRUM, BS .
EPILEPSY RESEARCH, 1991, 9 (02) :92-96
[3]  
COLLINS RL, 1972, EXPT MODELS EPILEPSY, P347
[4]   7,8-methylenedioxy-4H-2,3-benzodiazepin-4-ones as novel AMPA receptor antagonists [J].
De Sarro, A ;
De Sarro, G ;
Gitto, R ;
Grasso, S ;
Micale, N ;
Quartarone, S ;
Zappala, M .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (08) :971-976
[5]   Synthesis and anticonvulsant activity of new 2,3-benzodiazepines as AMPA receptor antagonists [J].
De Sarro, A ;
De Sarro, G ;
Gitto, R ;
Grasso, S ;
Micale, N ;
Zappalà, M .
FARMACO, 1999, 54 (03) :178-187
[6]   EXCITATORY AMINO-ACID NEUROTRANSMISSION THROUGH BOTH NMDA AND NON-NMDA RECEPTORS IS INVOLVED IN THE ANTICONVULSANT ACTIVITY OF FELBAMATE IN DBA/2 MICE [J].
DESARRO, G ;
ONGINI, E ;
BERTORELLI, R ;
AGUGLIA, U ;
DESARRO, A .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 262 (1-2) :11-19
[7]   ANTICONVULSANT ACTIONS OF DS-103-282 - PHARMACOLOGICAL STUDIES IN RODENTS AND THE BABOON, PAPIO-PAPIO [J].
DESARRO, GB ;
CROUCHER, MJ ;
MELDRUM, BS .
NEUROPHARMACOLOGY, 1984, 23 (05) :525-530
[8]  
DONEVAN SD, 1994, J PHARMACOL EXP THER, V271, P25
[9]   GYKI 52466, A 2,3-BENZODIAZEPINE, IS A HIGHLY SELECTIVE, NONCOMPETITIVE ANTAGONIST OF AMPA/KAINATE RECEPTOR RESPONSES [J].
DONEVAN, SD ;
ROGAWSKI, MA .
NEURON, 1993, 10 (01) :51-59
[10]   SELECTIVE RELEASE OF GLUTAMATE FROM CEREBELLAR GRANULE CELLS DIFFERENTIATING IN CULTURE [J].
GALLO, V ;
CIOTTI, MT ;
COLETTI, A ;
ALOISI, F ;
LEVI, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (24) :7919-7923
123