A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Novel Non-Competitive Antagonists of Kainate GluK1/GluK2 Receptors
Tekijät: Kaczor AA, Kronbach C, Unverferth K, Pihlaja K, Wiinamaki K, Sinkkonen J, Kijkowska-Murak U, Wrobel T, Stachal T, Matosiuk D
Kustantaja: BENTHAM SCIENCE PUBL LTD
Julkaisuvuosi: 2012
Journal: Letters in Drug Design and Discovery
Tietokannassa oleva lehden nimi: LETTERS IN DRUG DESIGN & DISCOVERY
Lehden akronyymi: LETT DRUG DES DISCOV
Numero sarjassa: 10
Vuosikerta: 9
Numero: 10
Aloitussivu: 891
Lopetussivu: 898
Sivujen määrä: 8
ISSN: 1570-1808
Tiivistelmä
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.
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.
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