MGluR2 positive allosteric modulators: A patent review (2009-present)

Expert Opinion on Therapeutic Patents

Volumn 23, Issue 5, 2013, Pages 629-647

  Trabanco, Andrés A ^a   Cid, José María ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

Metabotropic glutamate receptor 2; MGlu2; Positive allosteric modulator; Potentiator

Indexed keywords

4 AMINOBUTYRIC ACID; AGENTS AFFECTING PROTEIN METABOLISM; AZD 8529; BIPHENYL INDANONE A; GLUTAMIC ACID; JNJ 40411813; LY 487379; METABOTROPIC RECEPTOR 2; METABOTROPIC RECEPTOR 2 AGONIST; METABOTROPIC RECEPTOR 3; METABOTROPIC RECEPTOR 3 AGONIST; METABOTROPIC RECEPTOR AGONIST; PLACEBO; POMAGLUMETAD METHIONIL; POSITIVE ALLOSTERIC MODULATOR; TALAGLUMETAD; UNCLASSIFIED DRUG;

AMYGDALOID NUCLEUS; DRUG INDUSTRY; DRUG STRUCTURE; GENERALIZED ANXIETY DISORDER; HIPPOCAMPUS; HUMAN; NONHUMAN; PANIC; PREFRONTAL CORTEX; REVIEW; SCHIZOPHRENIA;

ALLOSTERIC REGULATION; ANIMALS; BINDING SITES; BRAIN; DRUG DESIGN; GAMMA-AMINOBUTYRIC ACID; GLUTAMIC ACID; HUMANS; PATENTS AS TOPIC; RECEPTORS, METABOTROPIC GLUTAMATE;

EID: 84876562945     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2013.777043     Document Type: Review

References (121)

1. Niswender CM, Conn JP. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010;50:295-322
2. Pilc A, Chaki S, Nowak G, Witkin JM. Mood disorders: regulation by metabotropic glutamate receptors. Biochem Pharmacol 2008;75:997-1006
3. Luscher C, Huber KM. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 2010;65:445-59
4. Vinson PN, Conn PJ. Metabotropic glutamate receptors as therapeutic targets for schizophrenia. Neuropharmacology 2012;62:1461-72
5. Chiechio S, Nicoletti F. Metabotropic glutamate receptors and the control of chronic pain. Curr Opin Pharmacol 2012;12:28-34
6. Foster OM. Metabotropic glutamate receptor ligands as potential therapeutics for addiction. Curr Drug Abuse Rev 2009;2:83-98
7. Johnson KA, Conn PJ, Niswender CM. Glutamate receptors as therapeutic targets for Parkinson's disease. CNS Neurol Disord Drug Targets 2009;8:475-91
8. Watkins JC. L-glutamate as a central neurotransmitter: looking back. Biochem Soc Trans 2000;28:297-310
9. Kew JNC, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl) 2005;179:4-29 (Pubitemid 40576690)
10. Huang S, Cao J, Jiang M, et al. Interdomain movements in metabotropic glutamate receptor activation. Proc Natl Acad Sci USA 2011;108:15480-5
11. Pin JP, Galvez T, Prezeau L. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther 2003;98:325-54 (Pubitemid 36638547)
12. Brauner-Osborne H, Wellendorph P, Jensen AA. Structure, pharmacology and therapeutic prospects of family C G-protein coupled receptors. Curr Drug Targets 2007;8:169-84 (Pubitemid 46049458)
13. Cartmell J, Schoepp DD. Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 2000;75:889-907 (Pubitemid 30660476)
14. Ohishi H, Shigemoto R, Nakanishi S, Mizuno N. Distribution of the messenger RNA for metabotropic glutamate receptor, mGlu2, in the central nervous system of the rat. Neuroscience 1993;53:1009-18 (Pubitemid 23126097)
15. Richards G, Messer J, Malherbe P, et al. Distribution and abundance of metabotropic glutamate receptor subtype 2 in rat brain revealed by [3H] LY354740 binding in vitro and quantitative radioautography: correlation with the sites of synthesis, expression, and agonist stimulation of [35S]GTPS binding. J Comp Neurology 2005;487:15-27 (Pubitemid 40646949)
16. Gu G, Lorrain DS, Wei H, et al. Distribution of metabotropic glutamate 2 and 3 receptors in the rat forebrain: implication in emotional responses and central disinhibition. Brain Res 2008;1197:47-62
17. Ghose S, Gleason KA, Potts BW, et al. Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action? Am J Psychiatry 2009;166:812-20
18. Shigeyuki C, Hirohiko H. Targeting of metabotropic glutamate receptors for the treatment of schizophrenia. Curr Pharm Des 2011;17:94-102
19. Monn JA, Valli MJ, Massey SM, et al. Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo [3.1.0]hexane-2,6- dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties. J Med Chem 1997;40:528-37 (Pubitemid 27080033)
20. Swanson CJ, Bures M, Johson MP, et al. Glutamate Receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 2005;4:131-44 (Pubitemid 40277494)
21. Fell MJ, McKinzie DL, Monn JA, Svensson KA. Group II metabotropic glutamate receptor agonists and positive allosteric modulators as novel treatments for schizophrenia. Neuropharmacology 2012;62:1473-83
22. Levine L, Gaydos B, Sheehan D, et al. The mGlu2/3 receptor agonist, LY354740, reduces panic anxiety induced by a CO2 challenge in patients diagnosed with panic disorder. Neuropharmacology 2002;43:294
23. Dunayevich E, Erickson J, Levine L, et al. Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder. Neuropsychopharmacology 2008;33:1603-10 (Pubitemid 351684700)
24. Patil ST, Zhang L, Martenyi F, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med 2007;13:1102-7 (Pubitemid 47517511)
25. Fell MJ, McKinzie DL, Monn JA, Svensson KA. Group II metabotropic glutamate receptor agonists and positive allosteric modulators as novel treatments for schizophrenia. Neuropharrmacology 2012;62:1473-83
26. Lilly Stops Phase III development of pomaglumetad methionil for the treatment of Schizophrenia based on efficacy results. Eli Lilly and Co. 2012. Available from: https://investor. lilly.com/releaseDetail.cfm? ReleaseID=703018
27. Iacovelli L, Molinaro G, Battaglia G, et al. Regulation of group II metabotropic glutamate receptors by G protein-coupled receptor kinases: mGlu2 receptors are resistant to homologous desensitization. Mol Pharmacol 2009;75:991-1003
28. Lennon SM, Rivero G, Matharu A, et al. Metabotropic glutamate receptor mGlu2 is resistant to homologous agonist-induced desensitization but undergoes protein kinase C-mediated heterologous desensitization. Eur J Pharmacol 2010;649:29-37
29. Pin JP, Parmentier M-L, Prezeau L. Positive allosteric modulators for-aminobutyric acidB receptors open new routes for the development of drugs targeting family 3 G-protein-coupled receptors. Mol Pharmacol 2001;60:881-4 (Pubitemid 33027421)
30. Gjoni T, Urwyler S. Receptor activation involving positive allosteric modulation, unlike full agonism, does not result in GABAB receptor desensitization. Neuropharmacology 2008;55:1293-9
31. Urwyler S. Allosteric modulation of family C G-protein-coupled receptors: from molecular insights to therapeutic perspectives. Pharmacol Rev 2011;63:59-126
32. Johnson MP, Baez M, Jagdmann GE, et al. Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor: synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy) phenyl)-N-(2,2,2-trifluoroethylsulfonyl) pirid-3-ylmethylamine. J Med Chem 2003;46:3189-92 (Pubitemid 36842403)
33. Bonnefous C, Vernier J-M, Hutchinson JH, et al. Biphenylindanones: allosteric potentiators of metabotropic glutamate subtype 2 receptor. Bioorg Med Chem Lett 2005;15:4354-8 (Pubitemid 41188018)
34. Johnson MP, Barda D, Britton TC, et al. Metabotropic glutamate receptor 2 potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and psychosis model(s). Psychopharmacology (Berl) 2005;179:271-83 (Pubitemid 40576715)
35. Galici R, Echemendia NG, Rodriguez AL, Conn JP. A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity. J Pharmacol Exp Ther 2005;315:1181-7 (Pubitemid 41635406)
36. Galici R, Jones CK, Kamondanai H, et al. Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic-and anxiolytic-like effects in mice. J Pharmacol Exp Ther 2006;318:173-85
37. Sheffler DJ, Pinkerton AB, Dahl R, et al. Recent progress in the synthesis and characterization of group II metabotropic glutamate receptor allosteric modulators. ACS Chem Neurosci 2011;2:382-93
38. Trabanco AA, Cid JM, Lavreysen H, et al. Progress in the development of positive allosteric modulators of the metabotropic glutamate receptor 2. Curr Med Chem 2011;18:47-68
39. Pinkerton AB, Vernier J-M, Schaffhauser H, et al. Phenyl-tetrazolyl acetophenones: discovery of allosteric potentiators for the metabotropic glutamate 2 receptor. J Med Chem 2004;47:4595-9 (Pubitemid 39096845)
40. Pinkerton AB, Cube RV, Hutchinson JH, et al. Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: identification and synthesis of phenyl-tetrazolyl acetophenones. Bioorg Med Chem Lett 2004;14:5329-32 (Pubitemid 39348923)
41. Pinkerton AB, Cube RV, Hutchinson JH, et al. Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 2: 4-thiopyridyl acetophenones as non-tetrazole-containing mGlu2 receptor potentiators. Bioorg Med Chem Lett 2004;14:5867-72 (Pubitemid 39421534)
42. Cube RV, Vernier J-M, Hutchinson JH, et al. 3-(2-ethoxy-4-{4-[3-hydroxy- 2-methyl-4-(3-methylbutanoyl)phenoxy] butoxy}phenylpropanoic acid: a brain penetrant allosteric potentiator at the metabotropic glutamate receptor 2 (mGluR2). Bioorg Med Chem Lett 2005;15:2389-93 (Pubitemid 40523106)
43. Govek SP, Bonnefous C, Hutchinson JH, et al. Benzazoles as allosteric potentiators of metabotropic glutamate receptor 2 (mGluR2): efficacy in animal model for schizophrenia. Bioorg Med Chem Lett 2005;15:4068-72 (Pubitemid 41132663)
44. Cid JM, Duvey G, Cluzeau P, et al. Discovery of 1,5-disubstituted pyridines: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor. ACS Chem Neurosci 2010;1:788-95
45. Cid JM, Duvey G, Tresadern G, et al. Discovery of 1,4-disubstituted 3-cyano-2-pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor. J Med Chem 2012;55:2388-405
46. AstraZeneca AB and NPS Pharmaceuticals, Inc. Isoindolone compounds and their use as metabotropic glutamate receptor potentiators. WO02087; 2006
47. AstraZeneca AB and NPS Pharmaceuticals, Inc. Metabotropicglutamate- receptor-potentiating isoindolones. WO021308; 2007
48. AstraZeneca AB and NPS Pharmaceuticals, Inc. Pyrazolone compounds as metabotropic glutamate receptor agonists for the treatment of neurological and psychiatric disorders. WO030031; 2006
49. Janssen Pharmaceuticals N.V. and Addex Pharmaceuticals S.A. Novel thieno-pyridine and thieno-pyrimidine derivatives and their use as positive allosteric modulators of mGluR2-receptors. WO030031; 2006
50. Duplantier AJ, Efremov I, Candler J, et al. 3-Benzyl-1,3-oxazolidin-2- ones as mGluR2 positive allosteric modulators: hit to lead and lead optimization. Bioorg Med Chem Lett 2009;19:2524-9
51. Brnardic EJ, Fraley ME, Garbaccio RM, et al. 3-Aryl-5-phenoxymethyl-1,3- oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: hit-to-lead efforts. Bioorg Med Chem Lett 2010;20:3129-33
52. Zhang L, Rogers BN, Duplantier AJ, et al. 3-(Imidazolyl methyl)-3-aza-bicyclo [3.1.0]hexan-6-yl)methyl ethers: a novel series of mGluR2 positive allosteric modulators. Bioorg Med Chem Lett 2008;18:5493-6
53. D'Alessandro PL, Corti C, Roth A, et al. The identification of structurally novel, selective, orally bioavailable positive allosteric modulators of mGluR2. Bioorg Med Chem Lett 2010;20:759-62
54. Zhang L, Brodney MA, Candler J, et al. 1-[(1-Methyl-1H-imidazol-2-yl) methyl]4-phenylpiperidines as mGluR2 positive allosteric modulators for the treatment of psychosis. J Med Chem 2011;54:1724-39
55. Sanofi-Aventis. Substituted dihydro and tetrahydro oxazolopyrimidones, preparation and use thereof. WO112483; 2008
56. Rudd MT, McCauley JA. Positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (mGluR2). Curr Top Med Chem 2005;5:869-84 (Pubitemid 41282355)
57. Fraley ME. Positive allosteric modulators of the metabotropic glutamate receptor 2 for the treatment of schizophrenia. Expert Opin Ther Patents 2009;1259-75
58. ADZ8529 single ascending dose study (SAD). ClinicalTrials.gov. Available from: http://clinicaltrials.gov/show/NCT00755378
59. Study to assess the efficacy, safety, and tolerability of ADZ8529 in adult schizophrenia patients. ClinicalTrials.gov. Available from: http://clinicaltrials.gov/show/NCT00921804
60. The effects ADZ8529 on cognition and negative symptoms in schizophrenics. Available from: http://clinicaltrials.gov/show/NCT00986531
61. Available from: http://www.astrazeneca. com/Investors/financial- information/Financial-results/2010-Financial-results
62. Ketamine challenge study with JNJ-40411813 to investigate whether JNJ-40411813 versus placebo reduces psychosis-like symptoms, induced by infusion of a low dose of ketamine. Available from: http://clinicaltrials.gov/ct2/show/ NCT01101659; ClinicalTrials. gov Identifier. NCT01101659
63. Study to explore the Safety, Tolerability and Potential clinical efficacy of JNJ-40411813 in schizophrenic patients. Available from: http:// clinicaltrials.gov/show/NCT01323205
64. Study to evaluate the efficacy and overall safety and tolerability of treatment with adjunctive JNJ-40411813 compared to placebo in patients with MDD with anxiety symptoms being treated with an antidepressant. Available from: http://clinicaltrials.gov/show/NCT01582815
65. Vinso PN, Conn JP. Metabotropic glutamate receptors as therapeutic targets for schizophrenia. Neuropharmacology 2012;62:1461-72
66. Hovelsø N, Sotty F, Montezinho LP, et al. Therapeutic potential of metabotropic glutamate receptor modulators. Curr Neuropharmacol 2012;10:12-48
67. Abbott GmbH & Co. KG. Novel small molecule potentiators of metabotropic glutamate receptors I. US0245232; 2011
68. Abbott GmbH & Co. KG. Novel small molecule potentiators of metabotropic glutamate receptors. US0245247; 2011
69. AstraZeneca AB and NPS Pharmaceuticals, Inc. Isoindolone compounds and their use as metabotropic glutamate receptor potentiators. WO020879; 2006
70. AstraZeneca AB. Isoxazole derivatives and their use as metabotropic glutamate receptor potentiators. WO148403; 2009
71. AstraZeneca AB. Polymorphs of metabotropic glutamate receptor positive allosteric modulator. WO136723; 2011
72. AstraZeneca AB. Oxadiazole derivatives and their use as metabotropic glutamate receptor potentiators. US0306077; 2008
73. Eli Lilly and Co. Imidazole carboxamides. WO009062; 2010
74. Fell MJ, Witkin JM, Falcone JF, et al. N-(4-((2-(trifluoromethyl)-3- hydroxy-4-(isobutyryl)phenoxy)methyl) benzyl)-1-methyl-1H-imidazole-4- carboxamide (THIIC), a novel metabotropic glutamate 2 potentiator with potential anxiolytic/antidepressant properties: In vivo profiling suggests a link between behavioral and central nervous system neurochemical change. JPET 2011;336:165-77
75. Johnson PL, Fitz SD, Engleman EA, et al. Group II metabotropic glutamate receptor type 2 allosteric potentiators prevent sodium lactate-induced panic-like response in panic-vulnerable rats. J Psychopharmacol 2013;27:152-61
76. Ortho-McNeil-Janssen Pharma, Inc. and Addex Pharmaceuticals S.A. 3-Azabicyclo [3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors. WO025890; 2010
77. Ortho-McNeil-Janssen Pharmaceuticals, Inc. and Addex Pharma S.A. Indole and benzomorpholine derivatives as modulators of metabotropic glutamate receptors. WO043396; 2010
78. Ortho-McNeil-Janssen Pharmaceuticals, Inc. and Addex Pharma S.A. Imidazo [1,2-a]pyridine derivatives as positive allosteric modulators of mGluR2 receptors. WO062676; 2009
79. Tresadern G, Cid J, Macdonald GJ, et al. Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor. Bioorg Med Chem Lett 2010;20:175-9
80. Ortho-McNeil-Janssen Pharmaceuticals, Inc. and Addex Pharma S.A. Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors. WO060589; 2010
81. Trabanco AA, Tresadern G, Macdonald GJ, et al. Imidazo[1,2-a] pyridines: orally active positive allosteric modulators of the metabotropic glutamate receptor 2. J Med Chem 2012;55:2688-701
82. Ahnaou A, Dautzenberg F, Geys H, et al. Modulation of group II metabotropic glutamate receptor (mGlu2) elicits common changes in rat and mice sleep-wake architecture. Eur J Pharmacol 2009;603:62-72
83. Ortho-McNeil-Janssen Pharmaceuticals, Inc. and Addex Pharma S.A. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors. WO130422; 2010
84. Ortho-McNeil-Janssen Pharmaceuticals, Inc. and Addex Pharma S.A. 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors. WO130423; 2010
85. Ortho-McNeil-Janssen Pharmaceuticals, Inc. and Addex Pharma S.A. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders. WO130424; 2010
86. Cid JM, Tresadern G, Vega JA, et al. Discovery of 3-cyclopropylmethyl-7- (4-phenyl-piperidin-1-yl)-8-trifluoromethyl [1,2,4]triazolo[4,3a] pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. J Med Chem 2012;55:8770-89
87. Janssen Pharmaceuticals, Inc. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors. WO062750; 2012
88. Janssen Pharmaceuticals, Inc. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors. WO062751; 2012
89. Janssen Pharmaceuticals, Inc. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors. WO062759; 2012
90. Janssen Pharmaceuticals, Inc. Radiolabelled mGluR2 PET ligands. WO062752; 2012
91. Andres J-I, Alcazar J, Cid JM, et al. Synthesis, evaluation, and radiolabeling of new potent positive allosteric modulators of the metabotropic glutamate receptor 2 as potential tracers for positron emission tomography imaging. J Med Chem 2012;55:8685-99
92. Merck & Co., Inc. 3,5-Substitured-1,3-oxazolidin-2-one derivatives. WO094265; 2009
93. Merck & Co., Inc. 3,5-Substitured-1,3-oxazolidin-2-one derivatives. US0292241; 2010
94. Merck & Co., Inc. Oxazolobenzimidazolone derivatives. WO140163; 2009
95. Merck & Co., Inc. Oxazolobenzimidazolone derivatives. WO140166; 2009
96. Garbaccio RM, Brnardic EJ, Fraley ME, et al. Discovery of oxazolobenzimidazoles as positive allosteric modulators for the mGluR2 receptor. ACS Med Chem Lett 2010;1:406-10
97. Merck & Co., Inc. Benzazole potentiators of metabotropic glutamate receptors. WO091496; 2006
98. Merck Sharp & Dohme Corp. Aminobenzotriazole derivatives. WO114726; 2010
99. Merck Sharp & Dohme Corp. Biaryl benzotriazole derivatives. WO141360; 2010
100. Merck Sharp & Dohme Corp. Ether benzotriazole derivatives. WO022312; 2011
101. Merck Sharp & Dohme Corp. Ether benzotriazole derivatives. US0135977; 2012
102. Merck Sharp & Dohme Corp. Aminomethyl biaryl benzotriazole derivatives. WO151136; 2012
103. Merck Sharp & Dohme Corp. Hydroxymethyl biaryl benzotriazole derivatives. WO151140; 2012
104. Merck Sharp & Dohme Corp. Cyclohenexe benzotriazole derivatives. WO151138; 2012
105. Merck Sharp & Dohme Corp. Alkyne benzotriazole derivatives. WO151139; 2012
106. Merck Sharp & Dohme Corp. Imidazopyridin-2-one derivatives. WO034741; 2011
107. Merck Sharp & Dohme Corp. Positive allosteric modulators of mGluR2. WO156245; 2011
108. Merck Sharp & Dohme Corp. Positive allosteric modulators of mGluR2. WO021382; 2012
109. Merck Sharp & Dohme Corp. Positive allosteric modulators of mGluR2. WO109277; 2011
110. Merck Sharp & Dohme Corp. Substituted 1,3-benzothiazol-2(3H)-ones and [1,3]thiazolo[5,4-b]pyridine-2(1H)-ones as positive allosteric modulators in mGluR2. WO137046; 2011
111. N.V. Organon. Heterocyclic derivatives. WO051490; 2011
112. Sanford-Burnham Medical Research Institute. Positive allosteric modulators of group II mGluRs. WO116356; 2011
113. Dhanya R-P, Sidique S, Sheffler DJ, et al. Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats. J Med Chem 2011;54:342-53
114. Sidique S, Dhanya R-P, Sheffler DJ, et al. Orally active metabotropic glutamate subtype 2 receptor positive allosteric modulators: structure-activity relationships and assessment in a rat model of nicotine dependence. J Med Chem 2012;55:9434-45
115. Sanofi-Aventis. Substituted dihydro, trihydro and tetrahydro cycloalkyloxazolopyrimidones, preparation and use thereof as allosteric modulators of mGluR. WO110901; 2009
116. Sanofi-Aventis. Substituted para-biphenyloxymethyl dihydro oxazolopyrimidones, preparation and use thereof. WO034828; 2011
117. Sanofi-Aventis. Substituted benzocycloalkyloxymethyl oxazolopyrimidones, preparation and use thereof. WO034830; 2011
118. Sanofi-Aventis. Substituted phenoxymethyl dihydro oxazolopyrimidones, preparation and use thereof. WO034832; 2011
119. Woolley ML, Pemberton DJ, Bate S, et al. The mGlu2 but not the mGlu3 receptor mediates the actions of the mGluR2/3 agonist, LY379268, in mouse models predictive of antipsychotic activity. Psychopharmacology (Berl) 2008;196:431-40
120. Linden AM, Johnson BG, Trokovic N, et al. Use of mGluR2 and mGluR3 knockout mice to explore in vivo receptor specificity of the mGluR2/3 selective agonist LY341495. Neuropharmacology 2009;57:172-82
121. Fell MJ, Svensson KA, Kjell A, et al. Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (-)-(1R,4S,5S,6S)-4- amino-2-sulphonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039). J Pharmacol Exp Ther 2008;326:209-17 (Pubitemid 351872145)