New non competitive AMPA antagonists

Gizella Ábrahám, Sándor Sólyom, Emese Csuzdi, Pál Berzsenyi, István Ling, István Tarnawa, Tamás Hámori, István Pallagi, Katalin Horváth, Ferenc Andrási, Gábor Kapus, László G. Hársing, István Király, Miklós Patthy, Gyula Horváth

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New halogen atom substituted 2,3-benzodiazepine derivatives condensed with an azole ring on the seven membered part of the ring system of type 3 and 4 as well as 5 and 6 were synthesized. It was found that chloro-, dichloro- and bromo-substitutions in the benzene ring and additionally imidazole ring condensation on the diazepine ring can successfully substitute the methylenedioxy group in the well known molecules GYKI 52466 (1) and GYKI 53773 (2) and the 3-acetyl-4-methyl structural feature in 2, respectively, preserving the highly active AMPA antagonist characteristic of the original molecules. From the most active compounds (3b,i) 3b (GYKI 47261) was chosen for detailed investigations. 3b revealed an excellent, broad spectrum anticonvulsant activity against seizures evoked by electroshock and different chemoconvulsive agents indicating a possible antiepileptic efficacy. 3b was found to be highly active in a transient model of focal ischemia predictive of a therapeutic value in human stroke. 3b also reversed the dopamine depleting effect of MPTP and antagonized the oxotremorine induced tremor in mice indicating a potential antiparkinson activity. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)2127-2143
Number of pages17
JournalBioorganic and Medicinal Chemistry
Issue number8
Publication statusPublished - Aug 1 2000


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Ábrahám, G., Sólyom, S., Csuzdi, E., Berzsenyi, P., Ling, I., Tarnawa, I., Hámori, T., Pallagi, I., Horváth, K., Andrási, F., Kapus, G., Hársing, L. G., Király, I., Patthy, M., & Horváth, G. (2000). New non competitive AMPA antagonists. Bioorganic and Medicinal Chemistry, 8(8), 2127-2143.