Novel Non-Competitive Antagonists of Kainate GluK1/GluK2 Receptors

Author(s): Agnieszka Anna Kaczor, Christiane Kronbach, Klaus Unverferth, Kalevi Pihlaja, Kirsti Wiinamaki, Jari Sinkkonen, Urszula Kijkowska-Murak, Tomasz Wrobel, Tomasz Stachal, Dariusz Matosiuk

Journal Name: Letters in Drug Design & Discovery

Volume 9 , Issue 10 , 2012

Become EABM
Become Reviewer
Call for Editor


A series of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles is synthesized by Fisher or Bischler method, followed by alkylation with an appropriate alkyl or aryl halide. Two compounds exhibit non-competitive antagonism towards GluK1 and six – towards GluK2 receptor. The values of IC50 are in micromolar range. The investigated compounds belong to the most active GluK1 non-competitive inhibitors and are the first known negative allosteric modulators of GluK2 receptor. The observed pattern of activity is rationalized by molecular modelling, in particular by construction of the pharmacophore model.

Keywords: Allosteric modulators, Indole derivatives, Glutamate receptors, Kainate receptors, Molecular modelling, Non-competitive antagonists of kainate receptors, ionotropic glutamate receptors, Alzheimer’s disease, NMDA receptor antagonists, Zindoxifene

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2012
Published on: 24 October, 2012
Page: [891 - 898]
Pages: 8
DOI: 10.2174/1570180811209050891
Price: $65

Article Metrics

PDF: 14