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
    Anderson, BA
    Harn, NK
    Hansen, MM
    Harkness, AR
    Lodge, D
    Leander, JD
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (14) : 1953 - 1956
  • [2] THE ANTICONVULSANT EFFECT OF THE NON-NMDA ANTAGONISTS, NBQX AND GYKI-52466, IN MICE
    CHAPMAN, AG
    SMITH, SE
    MELDRUM, BS
    [J]. 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
    De Sarro, A
    De Sarro, G
    Gitto, R
    Grasso, S
    Micale, N
    Quartarone, S
    Zappala, M
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (08) : 971 - 976
  • [5] Synthesis and anticonvulsant activity of new 2,3-benzodiazepines as AMPA receptor antagonists
    De Sarro, A
    De Sarro, G
    Gitto, R
    Grasso, S
    Micale, N
    Zappalà, M
    [J]. 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
    DESARRO, G
    ONGINI, E
    BERTORELLI, R
    AGUGLIA, U
    DESARRO, A
    [J]. 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
    DESARRO, GB
    CROUCHER, MJ
    MELDRUM, BS
    [J]. 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
    DONEVAN, SD
    ROGAWSKI, MA
    [J]. NEURON, 1993, 10 (01) : 51 - 59
  • [10] SELECTIVE RELEASE OF GLUTAMATE FROM CEREBELLAR GRANULE CELLS DIFFERENTIATING IN CULTURE
    GALLO, V
    CIOTTI, MT
    COLETTI, A
    ALOISI, F
    LEVI, G
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1982, 79 (24): : 7919 - 7923
123