Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides

István Borza, Éva Bozó, Gizella Barta-Szalai, Csilla Kiss, G. Tárkányi, Ádám Demeter, Tamás Gáti, Viktor Háda, Sándor Kolok, Anikó Gere, László Fodor, József Nagy, Kornél Galgóczy, Ildikó Magdó, B. Ágai, J. Fetter, Ferenc Bertha, György M. Keserü, Csilla Horváth, Sándor FarkasIstván Greiner, György Domány

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

(4-Benzylpiperidine-1-yl)-(6-hydroxy-1H-indole-2-yl)-methanone (6a) derived from (E)-1 -(4-benzylpiperidin-1-yl)-3-(4-hydroxy-phenyl)-propenone (5) was identified as a potent NR2B subunit-selective antagonist of the NMDA receptor. To establish the structure-activity relationship (SAR) and to attempt the improvement of the ADME properties of the lead, a series of compounds were prepared and tested. Several derivatives showed low nanomolar activity both in the binding and in the functional assay. In a formalin-induced hyperalgesia model in mice, 6a and (4-benzylpiperidine-1-yl)-[5(6)-hydroxy-1H-benzimidazol-2- yl]-methanone (60a) were as active as besonprodil (2) after oral administration. A CoMS1A model was developed based on binding data of a series of indole- and benzimidazole-2-carboxamides.

Original languageEnglish
Pages (from-to)901-914
Number of pages14
JournalJournal of Medicinal Chemistry
Volume50
Issue number5
DOIs
Publication statusPublished - Mar 8 2007

Fingerprint

N-Methyl-D-Aspartate Receptors
Hyperalgesia
Structure-Activity Relationship
Formaldehyde
Oral Administration
Assays
Derivatives
1-benzylpiperidine
indole
benzimidazole
2-hydroxy benzimidazole
Lead
besonprodil

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. / Borza, István; Bozó, Éva; Barta-Szalai, Gizella; Kiss, Csilla; Tárkányi, G.; Demeter, Ádám; Gáti, Tamás; Háda, Viktor; Kolok, Sándor; Gere, Anikó; Fodor, László; Nagy, József; Galgóczy, Kornél; Magdó, Ildikó; Ágai, B.; Fetter, J.; Bertha, Ferenc; Keserü, György M.; Horváth, Csilla; Farkas, Sándor; Greiner, István; Domány, György.

In: Journal of Medicinal Chemistry, Vol. 50, No. 5, 08.03.2007, p. 901-914.

Research output: Contribution to journalArticle

Borza, I, Bozó, É, Barta-Szalai, G, Kiss, C, Tárkányi, G, Demeter, Á, Gáti, T, Háda, V, Kolok, S, Gere, A, Fodor, L, Nagy, J, Galgóczy, K, Magdó, I, Ágai, B, Fetter, J, Bertha, F, Keserü, GM, Horváth, C, Farkas, S, Greiner, I & Domány, G 2007, 'Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides', Journal of Medicinal Chemistry, vol. 50, no. 5, pp. 901-914. https://doi.org/10.1021/jm060420k
Borza, István ; Bozó, Éva ; Barta-Szalai, Gizella ; Kiss, Csilla ; Tárkányi, G. ; Demeter, Ádám ; Gáti, Tamás ; Háda, Viktor ; Kolok, Sándor ; Gere, Anikó ; Fodor, László ; Nagy, József ; Galgóczy, Kornél ; Magdó, Ildikó ; Ágai, B. ; Fetter, J. ; Bertha, Ferenc ; Keserü, György M. ; Horváth, Csilla ; Farkas, Sándor ; Greiner, István ; Domány, György. / Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 5. pp. 901-914.
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AU - Barta-Szalai, Gizella

AU - Kiss, Csilla

AU - Tárkányi, G.

AU - Demeter, Ádám

AU - Gáti, Tamás

AU - Háda, Viktor

AU - Kolok, Sándor

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AU - Fodor, László

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AU - Galgóczy, Kornél

AU - Magdó, Ildikó

AU - Ágai, B.

AU - Fetter, J.

AU - Bertha, Ferenc

AU - Keserü, György M.

AU - Horváth, Csilla

AU - Farkas, Sándor

AU - Greiner, István

AU - Domány, György

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