Negative allosteric modulators (NAMs) of GluN2B-containing NMDARs provide pharmacological tools for the treatment of chronic neurodegenerative diseases. Novel NAMs have been designed on the basis of computational studies focused on the 'hit compound' 3. This series of indoles has been tested in competition assay. Compounds 16 and 17 were the most active ligands (IC50 values of 83 nM and 71 nM, respectively) and they showed a potency close to that of reference compounds ifenprodil (1, IC50 = 47 nM) and 3 (IC50 = 25 nM). Furthermore, docking studies have been performed for active ligand 16 and the results were in a good agreement with biological data. (C) 2016 Elsevier Ltd. All rights reserved.
Negative allosteric modulators (NAMs) of GluN2B-containing NMDARs provide pharmacological tools for the treatment of chronic neurodegenerative diseases. Novel NAMs have been designed on the basis of computational studies focused on the 'hit compound' 3. This series of indoles has been tested in competition assay. Compounds 16 and 17 were the most active ligands (IC50 values of 83 nM and 71 nM, respectively) and they showed a potency close to that of reference compounds ifenprodil (1, IC50 = 47 nM) and 3 (IC50 = 25 nM). Furthermore, docking studies have been performed for active ligand 16 and the results were in a good agreement with biological data. (C) 2016 Elsevier Ltd. All rights reserved.
Structure-guided design of new indoles as negative allosteric modulators (NAMs) of N-methyl-D-aspartate receptor (NMDAR) containing GluN2B subunit
Russo E;De Sarro G
2016-01-01
Abstract
Negative allosteric modulators (NAMs) of GluN2B-containing NMDARs provide pharmacological tools for the treatment of chronic neurodegenerative diseases. Novel NAMs have been designed on the basis of computational studies focused on the 'hit compound' 3. This series of indoles has been tested in competition assay. Compounds 16 and 17 were the most active ligands (IC50 values of 83 nM and 71 nM, respectively) and they showed a potency close to that of reference compounds ifenprodil (1, IC50 = 47 nM) and 3 (IC50 = 25 nM). Furthermore, docking studies have been performed for active ligand 16 and the results were in a good agreement with biological data. (C) 2016 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
