AMPA receptor positive allosteric modulators: A patent review

Expert Opinion on Therapeutic Patents

Volumn 23, Issue 5, 2013, Pages 615-628

  Pirotte, Bernard ^a   Francotte, Pierre ^a   Goffin, Eric ^a   De Tullio, Pascal ^a  

^a UNIVERSITY OF LIÈGE   (Belgium)

Author keywords

Alzheimer's disease; AMPA receptor modulators; Depression; Glutamate; Learning memory deficits; Neurological disorders; Positive allosteric modulators; Schizophrenia

Indexed keywords

1,4 BENZODIOXAN 6 CARBOXYLIC ACID PIPERIDIDE; 2,3 DIHYDRO 3,4 CYCLOPENTANO 1,2,4 BENZOTHIADIAZINE 1,1 DIOXIDE; 3 TRIFLUOROMETHYLPYRAZOLE DERIVATIVE; 6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; 7 CHLORO 3,4 DIHYDRO 3 METHYL 2H 1,2,4 BENZOTHIADIAZINE 1,1 DIOXIDE; AMPA RECEPTOR; ANIRACETAM; BENZAMIDE DERIVATIVE; BENZOTHIADIAZEPINE DIOXIDE; BENZOTHIADIAZINE DERIVATIVE; BENZOTHIADIAZINE DIOXIDE; BENZOXATHIAZEPINE DIOXIDE; CARBOXYLIC ACID; CX 1632; CX 614; CYCLOTHIAZIDE; DIAZOXIDE; FARAMPATOR; N [2 [4 (3 THIENYL)PHENYL]PROPYL] 2 PROPANESULFONAMIDE; N BIARYL (CYCLO) ALKYL 2 PROPANESULFONAMIDE DERIVATIVE; ORG 26576; PHENYLIMINOTHIAZOLE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRROLE DERIVATIVE; SULFONAMIDE; THENOIC ACID; THIADIAZINE DERIVATIVE; THIAZOLE DERIVATIVE; THIOCHROMAN DIOXIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; AUTISM; DEPRESSION; DRUG ACTIVITY; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; MILD COGNITIVE IMPAIRMENT; NONHUMAN; REVIEW; SCHIZOPHRENIA; SLEEP DISORDERED BREATHING;

ALLOSTERIC REGULATION; ANIMALS; DRUG DESIGN; HUMANS; MOLECULAR TARGETED THERAPY; NERVOUS SYSTEM DISEASES; PATENTS AS TOPIC; RECEPTORS, AMPA; SIGNAL TRANSDUCTION;

EID: 84876553053     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2013.770840     Document Type: Review

References (93)

1. Francotte P, de Tullio P, Fraikin P, et al. In search of novel AMPA potentiators. Recent Pat CNS Drug Discov 2006;1:239-46
2. Palmer CL, Cotton L, Henley JM. The molecular pharmacology and cell biology of R-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacol Rev 2005;57:253-77 (Pubitemid 41043886)
3. Mansour M, Nagarajan N, Nehring RB, et al. Heteromeric AMPA receptors assemble with a preferred subunit stoichiometry and spatial arrangement. Neuron 2001;32:841-53 (Pubitemid 34024845)
4. Robert A, Irizarry SN, Hughes TE, Howe JR. Subunit interactions and AMPA receptor desensitization. J Neurosci 2001;21:5574-86 (Pubitemid 32692156)
5. Greger IH, Esteban JA. AMPA receptor biogenesis and trafficking. Curr Opin Neurobiol 2007;17:289-97 (Pubitemid 46880326)
6. Armstrong N, Gouaux E. Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron 2000;28:165-81
7. Gouaux E. Structure and function of AMPA receptors. J Physiol 2004;554:249-53 (Pubitemid 38185776)
8. Collingridge GL, Isaac JT, Wang YT. Receptor trafficking and synaptic plasticity. Nat Rev Neurosci 2004;5:952-62 (Pubitemid 39593358)
9. Sommer B, Keinanen K, Verdoorn TA, et al. Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science 1990;249:1580-5
10. O'Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES. AMPA receptor potentiators for the treatment of CNS disorders. Curr Drug Targets CNS Neurol Disord 2004;3:181-94 (Pubitemid 38854913)
11. O'Neill MJ, Dix S. AMPA receptor potentiators as cognitive enhancers. IDrugs 2007;10:185-92 (Pubitemid 46438427)
12. Zarate CA Jr, Manji HK. The role of AMPA receptor modulation in the treatment of neuropsychiatric diseases. Exp Neurol 2008;211:7-10
13. Hashimoto K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 2009;61:105-23
14. Pirotte B, Francotte P, Goffin E, et al. Ring-fused thiadiazines as core structures for the development of potent AMPA receptor potentiators. Curr Med Chem 2010;17:3575-82
15. Ward SE, Harries M. Recent advances in the discovery of selective AMPA receptor positive allosteric modulators. Curr Med Chem 2010;17:3503-13
16. Dicou E, Rangon CM, Guimiot F, et al. Positive allosteric modulators of AMPA receptors are neuroprotective against lesions induced by an NMDA agonist in neonatal mouse brain. Brain Res 2003;970:221-5 (Pubitemid 36423198)
17. Alt A, Nisenbaum ES, Bleakman D, Witkin JM. A role for AMPA receptors in mood disorders. Biochem Pharmacol 2006;71:1273-88
18. Goff DC, Leahy L, Berman I, et al. A placebo-controlled pilot study of the ampakine CX516 adxded to clozapine in schizophrenia. J Clin Psychopharmacol 2001;21:484-7 (Pubitemid 32937430)
19. Lynch G. AMPA receptor modulators as cognitive enhancers. Curr Opin Pharmacol 2004;4:4-11 (Pubitemid 38145831)
20. Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 2008;7:426-37 (Pubitemid 351619114)
21. Adler LA, Kroon RA, Stein M, et al. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator Org 26576 in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 2012;72:971-7
22. Siegel GJ, Chauhan NB. Neurotrophic factors in Alzheimer's and Parkinson's disease brain. Brain Res Rev 2000;33:199-227
23. Lauterborn JC, Lynch G, Vanderklish P, et al. Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons. J Neurosci 2000;20:8-21 (Pubitemid 30220486)
24. Lauterborn JC, Truong GS, Baudry M, et al. Chronic elevation of brain-derived neurotrophic factor by ampakines. J Pharmacol Exp Ther 2003;307:297-305 (Pubitemid 37151921)
25. Lauterborn JC, Pineda E, Chen LY, et al. Ampakines cause sustained increases in brain-derived neurotrophic factor signaling at excitatory synapses without changes in AMPA receptor subunit expression. Neuroscience 2009;159:283-95
26. Mellor IR. The AMPA receptor as a therapeutic target: current perspectives and emerging possibilities. Fut Med Chem 2010;5:877-91
27. Morrow JA, Maclean JKF, Jamieson C. Recent advances in positive allosteric modulators of the AMPA receptor. Curr Opin Drug Discov Dev 2006;9:571-9 (Pubitemid 44378825)
28. Francotte P, de Tullio P, Pirotte B. Novel dipyrazoles acting as glutamate modulators. Expert Opin Ther Patents 2007;17:1489-93
29. O'Neill MJ, Witkin JM. AMPA receptor potentiators: application for depression and parkinson's disease. Curr Drug Targets 2007;8:603-20 (Pubitemid 46794920)
30. Arai AC, Kessler M. Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Curr Drug Targets 2007;583-602 (Pubitemid 46785059)
31. Sun MK. The quest for treatment of cognitive impairment: AMPA and mGlu5 receptor modulators. Expert Opin Ther Patents 2008;18:999-1010
32. Ward SE, Bax BD, Harries M. Challenges for and current status of research into positive modulators of AMPA receptors. Brit J Pharmacol 2010;160:181-90
33. Grove SJA, Jamieson C, Maclean JKF, et al. Positive allosteric modulators of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. J Med Chem 2010;53:7271-9
34. Clinical trials on CX516 and CX691 (Org 24448). Available from: http://www.clinicaltrials.gov/ct2/results? term=CX516&Search=Search [Last accessed 21 January 2013], http://www. clinicaltrials.gov/ct2/results?term=org +24448&Search=Search [Last accessed 21 January 2013]
35. Servier Exercises Option to Cortex's AMPAKINE-CX1632, An Innovative Compound in Clinical Development for Alzheimer's Disease. Available from: http://www.businesswire.com/news/home/20111006005361/en/Servier-Exercises- Option-Cortex's-AMPAKINE-CX1632-Innovative [Last accessed 21 January 2013]
36. Lipina T, Weiss K, Roder J. The ampakine CX546 restores the prepulse inhibition and latent inhibition deficits in mGluR5-deficient mice. Neuropsychopharmacology 2007;32:745-56 (Pubitemid 46426185)
37. Mueller R, Li YX, Hampson A, et al. Benzoxazinones as potent positive allosteric AMPA receptor modulators: part I. Bioorg Med Chem Lett 2001;21:3923-6
38. Cortex Pharmaceuticals, Inc.; Mueller R, Lee S, O'Hare S, et al. 3-Substituted-[1,2,3]benzotriazinone compounds for enhancing glutamatergic synaptic responses. WO085505; 2008
39. Cortex Pharmaceuticals, Inc.; Cordi A, Rogers G, Mueller R. 3-Substituted-[1,2,3]-benzotriazinone compound for enhancing glutamatergic synaptic responses. WO085506; 2008
40. Cortex Pharmaceuticals, Inc.; Mueller R, Street L, Rachwal S, Alisala K. 3-Substituted 1,2,3-triazin-4-one's and 3-substituted 1,3-pyrimidinone's for enhancing glutamatergic synaptic responses. WO038752; 2009
41. Adler LA, Kroon RA, Stein M, et al. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator Org 26576 in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 2012;72:971-7
42. Mueller R, Rachwal S, Tedder ME, et al. Substituted benzoxazinones as potent positive allosteric AMPA receptor modulators: part II. Bioorg Med Chem Lett 2011;21:3927-30
43. Mueller R, Rachwal S, Varney MA, et al. Benzotriazinone and benzopyrimidinone derivatives as potent positive allosteric AMPA receptor modulators. Bioorg Med Chem Lett 2011;21:7455-9
44. Pirotte B, Fontaine J, Lebrun P. Recent advances in the chemistry of potassium channel openers. Curr Med Chem 1995;2:573-82
45. Yamada KA, Rothman SM. Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons. J Physiol 1992;458:409-23 (Pubitemid 23024600)
46. Randle JC, Biton C, Lepagnol JM. Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials. Eur J Pharmacol 1993;247:257-65
47. Yamada KA, Tang CM. Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents. J Neurosci 1993;13:3904-15 (Pubitemid 23264374)
48. Bertolino M, Baraldi M, Parenti C, et al. Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus. Receptors Channels 1993;1:267-78 (Pubitemid 2036636)
49. Zivkovic I, Thompson DM, Bertolino M, et al. 7-Chloro-3-methyl-3-4- dihydro-2H-1,2,4-benzothiadiazine S, S-dioxide (IDRA 21): a benzothiadiazine derivative that enhances cognition by attenuating DL-alpha-amino-2,3-dihydro-5- methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor desensitization. J Pharmacol Exp Ther 1995;272:300-9
50. Thompson DM, Guidotti A, DiBella M, Costa E. 7-Chloro-3-methyl-3,4- dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys. Proc Natl Acad Sci USA 1995;92:7667-71
51. Francotte P, de Tullio P, Goffin E, et al. Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors. J Med Chem 2007;50:3153-7 (Pubitemid 47001258)
52. Pirotte B, Podona T, Diouf O, et al. 4H-1,2,4-Pyridothiadiazine 1,1-dioxides and 2,3-dihydro-4H-1,2,4-pyridothiadiazine 1,1-dioxides chemically related to diazoxide and cyclothiazide as powerful positive allosteric modulators of (R/S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid receptors: design, synthesis, pharmacology, and structure-activity relationships. J Med Chem 1998;41:2946-59 (Pubitemid 28359930)
53. Les Laboratoires Servier. Graindorge E, Francotte P, Boverie S, et al. Novel thiadiazine derivatives useful as AMPA receptor modulators, preparation method, and pharmaceutical compositions containing them. FR2854634; 2004
54. Phillips D, Sonnenberg J, Arai AC, et al. 5¢-Alkyl- benzothiadiazides: a new subgroup of AMPA receptor modulators with improved affinity. Bioorg Med Chem 2002;10:1229-48 (Pubitemid 34214688)
55. Krintel C, Frydenvang K, Olsen L, et al. Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2. Biochem J 2012;441:173-8
56. Les Laboratoires Servier; Pirotte B, de Tullio P, Boverie S, et al. Novel benzothiadiazine dioxide derivatives useful as AMPA receptor modulators, preparation method, and pharmaceutical compositions containing them. WO040210; 2001
57. Les Laboratoires Servier; Francotte P, Fraikin P, de Tullio P, et al. Preparation of fluorinated benzothiadiazine derivatives and their use as AMPA receptor modulators. EP1557412; 2005
58. Francotte P, Goffin E, Fraikin P, et al. New fluorinated 1,2,4-benzothiadiazine 1,1-dioxides: discovery of an orally active cognitive enhancer acting through potentiation of the 2-amino-3-(3-hydroxy-5- methylisoxazol-4-yl)propionic acid receptors. J Med Chem 2010;53:1700-11
59. Les Laboratoires Servier; Francotte P, de Tullio P, Pirotte B, et al. New cycloalkylated benzothiadiazine derivatives, method for preparing them and pharmaceutical compositions containing them. WO004139; 2010
60. Les Laboratoires Servier; de Tullio P, Pirotte B, Botez I, et al. Novel derivatives of cyclopropylated benzothiadiazines, method for preparing them and pharmaceutical compositions containing them. WO083265; 2011
61. Les Laboratoires Servier; Francotte P, de Tullio P, Pirotte B, et al. Thiochroman derivatives, method for preparing them and pharmaceutical compositions containing them. WO083264;2011
62. Les Laboratoires Servier; Cordi A, Desos P, Lestage P, Danober L. Benzothiadiazepine derivatives used as AMPA and NMDA receptor modulators. WO106249; 2010
63. Les Laboratoires Servier. Cordi A, Desos P, Lestage P, Danober L. Novel derivatives of dihydrobenzoxathiazepines, their preparation process and pharmaceutical compositions containing them. CA2752131; 2012
64. Universita'del Salento (IT)-Uniwersytet Medyczny W Lublinie (PL). Battisti U, Cannazza G, Puja G, et al. Derivatives of 1,2,4-benzothiadiazine dioxide, their preparation and use as allosteric modulators of the AMPA receptor. EP2457906; 2012
65. Battisti UM, Jozwiak K, Cannazza G, et al. 5-Arylbenzothiadiazine type compounds as positive allosteric modulators of AMPA/Kainate receptors. ACS Med Chem Lett 2012;3:25-9
66. Glaxo Group Ltd.; Bradley DM, Thewlis KM, Ward SE. Compounds which potentiate glutamate receptor and uses thereof in medicine. WO015828; 2006
67. Glaxo Group Ltd. Andreotti D, Arista L, Cardullo F, et al. Compounds which potentiate glutamate receptor and uses thereof in medicine. WO/087169; 2006
68. Glaxo Group Ltd.; Thewlis KM, Ward SE. 4-Phenyl-3-(2-propylsulfonylamino) tetrahydrofuran derivatives which potentiate glutamate receptors and are useful In the treatment of schizophrenia. WO/090840; 2007
69. Pfizer, Inc.; Estep KG, Fliri AFJ, O'Donnell CJ. Sulfonamides and pharmaceutical compositions thereof. WO120093; 2008
70. Gouaux JE, Song L, Xie Y, Landry DW. GluR2 receptor modulators. US0270508; 2009
71. N.V. Organon; Gillespie J, Jamieson C, Maclean JKF, et al. Indane derivatives as ampa receptor modulators. WO147167; 2009
72. N.V. Organon; Gillen KJ, Gillespie J, Jamieson C, et al. Indane derivatives. WO115952; 2010
73. Pfizer, Inc.; Estep KG, O'Donnell CJ, Xie L. Tetrahydrofuranyl sulfonamides for use as AMPA modulators in the treatment of CNS disorders. WO041162; 2010
74. Pfizer, Inc.; Fliri AFJ, Gallaschun RJ, O'Donnell CJ, et al. Heterocyclic sulfonamides, uses and pharmaceutical compositions thereof. WO150192; 2010
75. Ward SE, Harries M, Aldegheri L, et al. Discovery of N-[(2S)-5-(6-fluoro- 3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator. J Med Chem 2010;53:5801-12
76. Thewlis KM, Aldegheri L, Harries MH, et al. N-substituted pyrrolidines and tetrahydrofurans as novel AMPAR positive modulators. Bioorg Med Chem Lett 2010;20:7116-19
77. O'Donnell CJ. PF-4958242: A novel AMPA positive allosteric modulator (PAM) for the treatment of cognitive deficits associated with schizophrenia (MEDI 27). Division of Medicinal Chemistry 242nd ACS National Meeting, 28 August-1 September 2011, Denver, CO. Available from: http://www.acsmedchem.org/ mediabstractf2011.pdf
78. Fernandez MC, Castano A, Dominguez E, et al. A novel class of AMPA receptor allosteric modulators. Part 1: design, synthesis, and SAR of 3-aryl-4-cyano-5-substituted-heteroaryl-2-carboxylic acid derivatives. Bioorg Med Chem Lett 2006;16:5057-61 (Pubitemid 44247703)
79. Zarrinmayeh H, Tromiczak E, Zimmerman DM, et al. A novel class of positive allosteric modulators of AMPA receptors: design, synthesis, and structure-activity relationships of 3-biphenyl-4-yl-4-cyano-5-ethyl-1-methyl-1H- pyrrole-2-carboxylic acid, LY2059346. Bioorg Med Chem Lett 2006;16:5203-6 (Pubitemid 44247689)
80. Glaxo Group Ltd.; Bradley DM, Chan WN, Harrison S, et al. Compounds which potentiate AMPA receptor and uses thereof in medicine. WO122241; 2007
81. Glaxo Group Ltd.; Chan WN, Harrison S, Hughes OR, et al. Compounds which potentiate AMPA receptor and uses thereof in medicine. WO053448; 2009
82. Glaxo Group Ltd.; Chan WN, Thewlis KM, Ward SE. Thiazoles which potentiate AMPA receptor and medicinal uses thereof. WO053449; 2009
83. N.V. Organon; Gillen KJ, Jamieson C, Maclean JKF, et al. Pyrazolealkanamide substituted thiophenes as AMPA potentiators. WO003452; 2008
84. Organon USA, Inc.; Gallagher MG, Jamieson CC, Lyons AJ, et al. Heterocyclic derivatives. US0131455; 2009
85. Glaxo Group Ltd.; Bradley DM, Chan WN, Harrison S, et al. Compounds which potentiate AMPA receptor and uses thereof in medicine. WO107539; 2007
86. Glaxo Group Ltd.; Bradley DM, Chan WN, Thewlis KM, Ward SE. Compounds which potentiate AMPA receptor and uses thereof in medicine. WO053031; 2008
87. Glaxo Group Ltd.; Bertheleme N, Bradley DM, Cardullo F, et al. Compounds which potentiate AMPA receptor and uses thereof in medicine. WO113795; 2008
88. Glaxo Group Ltd.; Bradley DM, Chan WN, Ward SE. Compounds which potentiate AMPA receptor and uses thereof in medicine. WO148836; 2008
89. Takeda Pharmaceutical Co. Ltd.; Mochizuki M, Imaeda T. Heterocyclic compound. WO140339; 2010
90. Jamieson C, Basten S, Campbell RA, et al. A novel series of positive modulators of the AMPA receptor: discovery and structure based hit-to-lead studies. Bioorg Med Chem Lett 2010;20:5753-6
91. Jamieson C, Campbell RA, Cumming IA, et al. A novel series of positive modulators of the AMPA receptor: structure-based lead optimization. Bioorg Med Chem Lett 2010;20:6072-5
92. Jamieson C, Maclean JK, Brown CI, et al. Structure based evolution of a novel series of positive modulators of the AMPA receptor. Bioorg Med Chem Lett 2011;21:805-11
93. Ward SE, Harries M, Aldegheri L, et al. Integration of lead optimization with crystallography for a membrane-bound ion channel target: discovery of a new class of AMPA receptor positive allosteric modulators. J Med Chem 2011;54:78-94