Synthesis and Biological Characterization of 3-Substituted-1H-indoles as Ligands of GluN2B-Containing N-Methyl-D-aspartate Receptors

被引：18

作者：

Gitto, Rosaria ^{[1
]}

De Luca, Laura ^{[1
]}

Ferro, Stefania ^{[1
]}

Buemi, Maria Rosa ^{[1
]}

Russo, Emilio ^{[2
]}

De Sarro, Giovarnbattista ^{[2
]}

Costa, Lara ^{[3
]}

Ciranna, Lucia ^{[3
]}

Prezzavento, Orazio ^{[4
]}

Arena, Emanuela ^{[4
]}

Ronsisvalle, Simone ^{[4
]}

Bruno, Giuseppe ^{[5
]}

Chimirri, Alba ^{[1
]}

机构：

[1] Univ Messina, Dipartimento Farmacochim, I-98168 Messina, Italy

[2] Magna Graecia Univ Catanzaro, Dipartimento Med Sperimentale & Clin, I-88100 Catanzaro, Italy

[3] Univ Catania, Dipartimento Sci Biomed, Sez Fisiol, I-95125 Catania, Italy

[4] Univ Catania, Dipartimento Sci Farmaco, I-95125 Catania, Italy

[5] Univ Messina, Dipartimento Chim Inorgan Chim Analit & Chim Fis, I-98100 Messina, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 24期

关键词：

NMDA ANTAGONISTS; PHARMACOLOGY; SUBUNITS; CHANNELS; BINDING; DESIGN;

D O I：

10.1021/jm2008002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

As an extension of our studies, novel indole derivatives were rationally designed and synthesized as ligands targeted to GluN2B/NMDA receptors. The 2-(4-benzylpiperidin-1-yl)-1-(6-hydroxy-1H-indol-3-yl)ethanone (4i) and 1-(4-benzylpiperidin-l-yl)-2-(6-hydroxy-1H-indol-3-yl)ethane-1,2-dione (6i) showed high binding affinity in [H-3]ifenprodil displacement assay. By computational studies, we suggested the hypothetical interactions playing a significant role during the binding process. However, in functional and in vivo studies the most potent compound 4i did not show any activity whereas it displayed relevant affinity toward the sigma(2) receptor.

引用

页码：8702 / 8706

页数：5

共 50 条

[21] Enantiomerically Pure 2-Methyltetrahydro-3-benzazepin-1-ols Selectively Blocking GluN2B Subunit Containing N-Methyl-D-aspartate Receptors
Tewes, Bastian
Frehland, Bastian
Schepmann, Dirk
Robaa, Dina
Uenwetwanit, Tanaporn
Gaube, Friedemann
Winckler, Thomas
Sippl, Wolfgang
Wuensch, Bernhard
JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (15) : 6293 - 6305
[22] First-in-Humans Brain PET Imaging of the GluN2B-Containing N-methyl-D-aspartate Receptor with (R)-11C-Me-NB1
Rischka, Lucas
Vraka, Chrysoula
Pichler, Verena
Rasul, Sazan
Nics, Lukas
Gryglewski, Gregor
Handschuh, Patricia
Murgas, Matej
Godbersen, Godber M.
Silberbauer, Leo R.
Unterholzner, Jakob
Wotawa, Christoph
Haider, Ahmed
Ahmed, Hazem
Schibli, Roger
Mindt, Thomas
Mitterhauser, Markus
Wadsak, Wolfgang
Hahn, Andreas
Lanzenberger, Rupert
Hacker, Marcus
Ametamey, Simon M.
JOURNAL OF NUCLEAR MEDICINE, 2022, 63 (06) : 936 - 941
[23] GluN2A-and GluN2B-containing pre-synaptic N-methyl-D-aspartate receptors differentially regulate action potential-evoked Ca2+ influx via modulation of SK channels
Schmidt, Carla C.
Tong, Rudi
Emptage, Nigel J.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2024, 379 (1906)
[24] Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia
Chung, Connie
Marson, John D.
Zhang, Quan-Guang
Kim, Jimok
Wu, Wei-Hua
Brann, Darrell W.
Chen, Bo-Shiun
SCIENTIFIC REPORTS, 2016, 6
[25] Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia
Connie Chung
John D. Marson
Quan-Guang Zhang
Jimok Kim
Wei-Hua Wu
Darrell W. Brann
Bo-Shiun Chen
Scientific Reports, 6
[26] Unique Biology and Single-Channel Properties of GluN2A- and GluN2C-Containing Triheteromeric N-Methyl-D-Aspartate Receptors
Bhattacharya, Subhrajit
Traynelis, Stephen F.
JOURNAL OF EXPERIMENTAL NEUROSCIENCE, 2018, 12
[27] Glutamate Binding to the GluN2B Subunit Controls Surface Trafficking of N-Methyl-D-aspartate (NMDA) Receptors
She, Kevin
Ferreira, Joana S.
Carvalho, Ana Luisa
Craig, Ann Marie
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (33) : 27432 - 27445
[28] Residues in the GluN1 C-terminal domain control kinetics and pharmacology of GluN1/GluN3A N-methyl-D-aspartate receptors
Cummings, Kirstie A.
Belin, Sophie
Popescu, Gabriela K.
NEUROPHARMACOLOGY, 2017, 119 : 40 - 47
[29] GluN2D-Containing N-methyl-D-Aspartate Receptors Mediate Synaptic Transmission in Hippocampal Interneurons and Regulate Interneuron Activity
Perszyk, Riley E.
DiRaddo, John O.
Strong, Katie L.
Low, Chian-Ming
Ogden, Kevin K.
Khatri, Alpa
Vargish, Geoffrey A.
Pelkey, Kenneth A.
Tricoire, Ludovic
Liotta, Dennis C.
Smith, Yoland
McBain, Chris J.
Traynelis, Stephen F.
MOLECULAR PHARMACOLOGY, 2016, 90 (06) : 689 - 702
[30] Discovery of GluN2A subtype-selective N-methyl-D-aspartate (NMDA) receptor ligands
Jiang, Liyang
Liu, Na
Zhao, Fabao
Huang, Boshi
Kang, Dongwei
Zhan, Peng
Liu, Xinyong
ACTA PHARMACEUTICA SINICA B, 2024, 14 (05) : 1987 - 2005

← 1 2 3 4 5 →