Discovery of 1,5-Disubstituted Pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

被引：19

作者：

Maria Cid, Jose ^{[1
]}

Duvey, Guillaume ^{[2
]}

Cluzeau, Philippe ^{[2
]}

Nhem, Vanthea ^{[2
]}

Macary, Karim ^{[2
]}

Raux, Alexandre ^{[2
]}

Poirier, Nicolas ^{[2
]}

Muller, Jessica ^{[2
]}

Bolea, Christelle ^{[2
]}

Finn, Terry ^{[2
]}

Poli, Sonia ^{[2
]}

Epping-Jordan, Mark ^{[2
]}

Chamelot, Emilie ^{[2
]}

Derouet, Francis ^{[2
]}

Girard, Francoise ^{[2
]}

Macdonald, Gregor J. ^{[3
]}

Antonio Vega, Juan ^{[1
]}

Isabel de Lucas, Ana ^{[1
]}

Matesanz, Encarnacion ^{[1
]}

Lavreysen, Hilde ^{[4
]}

Lourdes Linares, Maria ^{[1
]}

Oehlrich, Daniel ^{[1
]}

Oyarzabal, Julen ^{[5
]}

Tresadern, Gary ^{[5
]}

Trabanco, Andres A. ^{[1
]}

Ignacio Andres, Jose ^{[1
]}

Le Poul, Emmanuel ^{[2
]}

Imogai, Hassan ^{[2
]}

Lutjens, Robert ^{[2
]}

Rocher, Jean-Philippe ^{[2
]}

机构：

[1] Janssen Cilag SA, Johnson & Johnson Pharmaceut Res & Dev, Neurosci Med Chem, Poligono Ind 45007, Toledo, Spain

[2] Addex Pharmaceut, CH-1228 Geneva, Switzerland

[3] Janssen Pharmaceut NV, Johnson & Johnson Pharmaceut Res & Dev, Neurosci Med Chem, B-2340 Beerse, Belgium

[4] Janssen Pharmaceut NV, Johnson & Johnson Pharmaceut Res & Dev, Neurosci, B-2340 Beerse, Belgium

[5] Janssen Cilag SA, Johnson & Johnson Pharmaceut Res & Dev, Res Informat, Poligono Ind 45007, Toledo, Spain

来源：

ACS CHEMICAL NEUROSCIENCE | 2010年 / 1卷 / 12期

关键词：

mGluR2; metabotropic; glutamate; allosteric; PAM; modulators; GLUTAMATE-RECEPTOR-2; MGLU2; POTENTIATORS; AGONIST; ACETOPHENONES; DISORDERS; LY354740; ANXIETY;

D O I：

10.1021/cn1000638

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice.

引用

页码：788 / 795

页数：8

共 50 条

[1] Discovery of 1,4-Disubstituted 3-Cyano-2-pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor
Maria Cid, Jose
Duvey, Guillaume
Tresadern, Gary
Nhem, Vanthea
Furnari, Rocco
Cluzeau, Philippe
Antonio Vega, Juan
Isabel de Lucas, Ana
Matesanz, Encarnacion
Manuel Alonso, Jose
Lourdes Linares, Maria
Ignacio Andres, Jose
Poli, Sonia M.
Lutjens, Robert
Himogai, Hassan
Rocher, Jean-Philippe
Macdonald, Gregor J.
Oehlrich, Daniel
Lavreysen, Hilde
Ahnaou, Abdelah
Drinkenburg, Wilhelmus
Mackie, Claire
Trabanco, Andres A.
JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (05) : 2388 - 2405
[2] Acyl dihydropyrazolo[1,5-a]pyrimidinones as metabotropic glutamate receptor 5 positive allosteric modulators
Malosh, Chrysa
Turlington, Mark
Bridges, Thomas M.
Rook, Jerri M.
Noetzel, Meredith J.
Vinson, Paige N.
Steckler, Thomas
Lavreysen, Hilde
Mackie, Claire
Bartolome-Nebreda, Jose M.
Conde-Ceide, Susana
Martinez-Viturro, Carlos M.
Piedrafita, Maria
Sanchez-Casado, M. Rosa
Macdonald, Gregor J.
Daniels, J. Scott
Jones, Carrie K.
Niswender, Colleen M.
Conn, P. Jeffrey
Lindsley, Craig W.
Stauffer, Shaun R.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (22) : 5115 - 5120
[3] Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor
Tresadern, Gary
Maria Cid, Jose
Macdonald, Gregor J.
Antonio Vega, Juan
Isabel de Lucas, Ana
Garcia, Aranzazu
Matesanz, Encarnacion
Lourdes Linares, Maria
Oehlrich, Daniel
Lavreysen, Hilde
Biesmans, Ilse
Trabanco, Andres A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (01) : 175 - 179
[4] Positive allosteric modulators of the metabotropic glutamate receptor 2 for the treatment of schizophrenia
Fraley, Mark E.
EXPERT OPINION ON THERAPEUTIC PATENTS, 2009, 19 (09) : 1259 - 1275
[5] Progress in the Developement of Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 2
Trabanco, A. A.
Cid, J. M.
Lavreysen, H.
Macdonald, G. J.
Tresadern, G.
CURRENT MEDICINAL CHEMISTRY, 2011, 18 (01) : 47 - 68
[6] Positive allosteric modulators of metabotropic glutamate receptor 5: A new generation of antipsychotics?
Mutel, V
Bessis, AS
Epping-Jordan, M
Le Poul, E
Ludwig, B
Poli, SM
Rocher, JP
NEUROPSYCHOPHARMACOLOGY, 2005, 30 : S30 - S30
[7] A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators
Hemstapat, Kamondanai
de Paulis, Tomas
Chen, Yelin
Brady, Ashley E.
Grover, Vandana K.
Alagille, David
Tamagnan, Gilles D.
Conn, P. Jeffrey
MOLECULAR PHARMACOLOGY, 2006, 70 (02) : 616 - 626
[8] Discovery of dihydropyrrolopyrazinone derivatives as metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs)
Tsuda, Yusuke
Fukaya, Takayuki
Masuda, Takahiro
Sugishita, Aiko
Sumitomo, Masako
Kitamura, Atsushi
Nishimura, Naohiro
Masumoto, Shuji
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2014, 247
[9] Pharmacological characterisation of positive allosteric modulators acting on the metabotropic glutamate receptor 2
Bennett, K. A.
Weaver, A.
Marshall, F.
Langmead, C. J.
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2013, 23 : S4 - S5
[10] Pharmacological and molecular characterization of the positive allosteric modulators of metabotropic glutamate receptor 2
Lundstrom, L.
Bissantz, C.
Beck, J.
Dellenbach, M.
Woltering, T. J.
Wichmann, J.
Gatti, S.
NEUROPHARMACOLOGY, 2016, 111 : 253 - 265

← 1 2 3 4 5 →