A new phenylalanine derivative acts as an antagonist at the AMPA Receptor GluA2 and introduces partial domain closure: Synthesis, resolution, pharmacology, and crystal structure

Journal of Medicinal Chemistry

Volumn 54, Issue 20, 2011, Pages 7289-7298

  Szymańska, Ewa ^a,b   Frydenvang, Karla ^a   Contreras Sanz, Alberto ^a   Pickering, Darryl S ^a   Frola, Elena ^a   Serafimoska, Zorica ^a   Nielsen, Birgitte ^a   Kastrup, Jette S ^a   Johansen, Tommy N ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3 [2 (2 CARBOXYETHYL) 4,5 DICHLOROPHENYL]PROPIONIC ACID; 2 AMINO 3 [2 (2 CARBOXYETHYL) 5 CHLORO 4 NITROPHENYL]PROPIONIC ACID; 2 AMINO 3 [2 (2 CARBOXYETHYL) 5 CHLOROPHENYL]PROPIONIC ACID; 2 AMINO 3 [2 (2 CARBOXYETHYL) 5 HYDROXYMETHYL]PROPIONIC ACID; 2 AMINO 3 [2 (2 CARBOXYETHYL) 5 METHYLPHENYL]PROPIONIC ACID; 2 AMINO 3 [2 (2 CARBOXYETHYL)PHENYL]PROPIONIC ACID; 2 AMINO 3 [4 AMINO 2 (2 CARBOXYETHYL) 5 CHLOROPHENYL]PROPIONIC ACID; 2 AMINO 3 [5 TERT BUTYL 2 (2 CARBOXYETHYL)PHENYL]PROPIONIC ACID; 2 AMINO 3 [6 (2 CARBOXYETHYL) 2,3 DICHLOROPHENYL]PROPIONIC ACID; 2 CARBOXYETHYLPHENYLALANINE DERIVATIVE; 4 (2 AMINO 2 CARBOXYETHYL) 5 (2 CARBOXYETHYL) 2 CHLOROBENZOIC ACID; AMPA RECEPTOR; AMPA RECEPTOR ANTAGONIST; AMPA RECEPTOR GLUA1; AMPA RECEPTOR GLUA2; PHENYLALANINE DERIVATIVE; PROPIONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; COMPETITIVE INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ELECTROPHYSIOLOGY; ENANTIOMER; HYDROGEN BOND; MOLECULAR INTERACTION; NONHUMAN; RADIOASSAY;

ANIMALS; BRAIN; CELL LINE; CIRCULAR DICHROISM; CRYSTALLOGRAPHY, X-RAY; FEMALE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OOCYTES; PHENYLALANINE; PROTEIN STRUCTURE, TERTIARY; RADIOLIGAND ASSAY; RATS; RECEPTORS, AMPA; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; XENOPUS LAEVIS;

EID: 80054907722     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200862h     Document Type: Article

References (33)

1. Traynelis, S. F.; Wollmuth, L. P.; McBain, C. J.; Menniti, F. S.; Vance, K. M.; Ogden, K. K.; Hansen, K. B.; Yuan, H.; Myers, S. J.; Dingledine, R. Glutamate receptor ion channels: structure, regulation, and function Pharmacol. Rev. 2010, 62, 405-496
2. Bleakman, D.; Alt, A.; Nisenbaum, E. S. Glutamate receptors and pain Semin. Cell Dev. Biol. 2006, 17, 592-604 (Pubitemid 46389351)
3. Black, M. D. Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data Psychopharmacology 2005, 179, 154-163 (Pubitemid 40584805)
4. Kew, J. N.; Kemp, J. A. Ionotropic and metabotropic glutamate receptor structure and pharmacology Psychopharmacology 2005, 179, 4-29 (Pubitemid 40576690)
5. Rao, V. R.; Finkbeiner, S. NMDA and AMPA receptors: old channels, new tricks Trends Neurosci. 2007, 30, 284-291 (Pubitemid 46802833)
6. Hume, R. I.; Dingledine, R.; Heinemann, S. F. Identification of a site in glutamate receptor subunits that controls calcium permeability Science 1991, 253, 1028-1031 (Pubitemid 21917250)
7. Lomeli, H.; Mosbacher, J.; Melcher, T.; Hoger, T.; Geiger, J. R.; Kuner, T.; Monyer, H.; Higuchi, M.; Bach, A.; Seeburg, P. H. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing Science 1994, 266, 1709-1713
8. Fleming, J. J.; England, P. M. Developing a complete pharmacology for AMPA receptors: a perspective on subtype-selective ligands Bioorg. Med. Chem. 2010, 18, 1381-1387
9. Jane, D. E.; Hoo, K.; Kamboj, R.; Deverill, M.; Bleakman, D.; Mandelzys, A. Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes J. Med. Chem. 1997, 40, 3645-3650 (Pubitemid 27465096)
10. Greenwood, J. R.; Mewett, K. N.; Allan, R. D.; Martin, B. O.; Pickering, D. S. 3-Hydroxypyridazine 1-oxides as carboxylate bioisosteres: a new series of subtype-selective AMPA receptor agonists Neuropharmacology 2006, 51, 52-59
11. Coquelle, T.; Christensen, J. K.; Banke, T. G.; Madsen, U.; Schousboe, A.; Pickering, D. S. Agonist discrimination between AMPA receptor subtypes NeuroReport 2000, 11, 2643-2648
12. Banke, T. G.; Greenwood, J. R.; Christensen, J. K.; Liljefors, T.; Traynelis, S. F.; Schousboe, A.; Pickering, D. S. Identification of amino acid residues in GluR1 responsible for ligand binding and desensitization J. Neurosci. 2001, 21, 3052-3062 (Pubitemid 32323487)
13. Hogner, A.; Kastrup, J. S.; Jin, R.; Liljefors, T.; Mayer, M. L.; Egebjerg, J.; Larsen, I. K.; Gouaux, E. Structural basis for AMPA receptor activation and ligand selectivity: crystal structures of five agonist complexes with the GluR2 ligand-binding core J. Mol. Biol. 2002, 322, 93-109 (Pubitemid 36138726)
14. Bjerrum, E. J.; Kristensen, A. S.; Pickering, D. S.; Greenwood, J. R.; Nielsen, B.; Liljefors, T.; Schousboe, A.; Brauner-Osborne, H.; Madsen, U. Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO) J. Med. Chem. 2003, 46, 2246-2249 (Pubitemid 36588362)
15. Hogner, A.; Greenwood, J. R.; Liljefors, T.; Lunn, M. L.; Egebjerg, J.; Larsen, I. K.; Gouaux, E.; Kastrup, J. S. Competitive antagonism of AMPA receptors by ligands of different classes: crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX J. Med. Chem. 2003, 46, 214-221 (Pubitemid 36082867)
16. Hamilton, G. S. Omega-[2-(alkyl)phenyl]-2-aminoalkanoic Acids as Antagonists of Excitatory Amino Acids Receptors. US 5,364,876, 1994.
17. Hamilton, G. S.; Huang, Z.; Patch, R. J.; Guzewska, M. E.; Elliott, R. L.; Borosky, S. A.; Bednar, D. L.; Ferkany, J. W.; Karbon, E. W. Phosphonoethylphenylalanine derivatives as novel antagonists of non-NMDA ionotropic glutamate receptors Bioorg. Med. Chem. Lett. 1992, 2, 1269-1274
18. Oi, N.; Kitahara, H.; Kira, R. Direct separation of enatiomers by high-performance liquid chromatography on a new chiral ligand-exchange phase J. Chromatogr., A 1992, 592, 291-296
19. Miyazawa, T.; Minowa, H.; Imagawa, K.; Yamada, T. Enantiomeric separation of non-protein amino acids by chiral ligand-exchange high-performance liquid chromatography Anal. Lett. 1997, 30, 867-882 (Pubitemid 27484342)
20. Armstrong, D. W.; Liu, Y.; Ekborg-Ott, K. H. A covalently bonded teicoplanin chiral stationary phase for HPLC enantioseparations Chirality 1995, 7, 474-497
21. Berthod, A.; Liu, Y.; Bagwill, C.; Armstrong, D. W. Facile liquid chromatographic enantioresolution of native amino acids and peptides using a teicoplanin chiral stationary phase J. Chromatogr., A 1996, 731, 123-137 (Pubitemid 26149015)
22. MØller, E. H.; Egebjerg, J.; Brehm, L.; StensbØl, T. B.; Johansen, T. N.; Madsen, U.; Krogsgaard-Larsen, P. Resolution, absolute stereochemistry, and enantiopharmacology of the GluR1-4 and GluR5 antagonist 2-amino-3-[5- tert -butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid Chirality 1999, 11, 752-759 (Pubitemid 29531972)
23. Madsen, U.; Brauner-Osborne, H.; Frydenvang, K.; Hvene, L.; Johansen, T. N.; Nielsen, B.; Sanchez, C.; StensbØl, T. B.; Bischoff, F.; Krogsgaard-Larsen, P. Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors J. Med. Chem. 2001, 44, 1051-1059 (Pubitemid 32861446)
24. Legrand, M.; Rougier, M. J. Application of the Optical Activity to Stereochemical Determinations. In Determination of Configurations by Dipole Moment, CD or ORD; Kaagan, H. B., Ed.; Stereochemistry: Fundamentals and Methods, Vol. 2; Georg Thieme Publishers: Stuttgart, Germany, 1977; pp 33-183.
25. Frandsen, A.; Pickering, D. S.; Vestergaard, B.; Kasper, C.; Nielsen, B. B.; Greenwood, J. R.; Campiani, G.; Fattorusso, C.; Gajhede, M.; Schousboe, A.; Kastrup, J. S. Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2 Mol. Pharmacol. 2005, 67, 703-713 (Pubitemid 40372239)
26. Ahmed, A. H.; Thompson, M. D.; Fenwick, M. K.; Romero, B.; Loh, A. P.; Jane, D. E.; Sondermann, H.; Oswald, R. E. Mechanisms of antagonism of the GluR2 AMPA receptor: structure and dynamics of the complex of two willardiine antagonists with the glutamate binding domain Biochemistry 2009, 48, 3894-3903
27. Madsen, U.; Bang-Andersen, B.; Brehm, L.; Christensen, I. T.; Ebert, B.; Kristoffersen, I. T.; Lang, Y.; Krogsgaard-Larsen, P. Synthesis and pharmacology of highly selective carboxy and phosphono isoxazole amino acid AMPA receptor antagonists J. Med. Chem. 1996, 39, 1682-1691 (Pubitemid 26124240)
28. PØhlsgaard, J.; Frydenvang, K.; Madsen, U.; Kastrup, J. S. Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators Neuropharmacology 2011, 60, 135-150
29. 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, 165-181
30. Menuz, K.; Stroud, R. M.; Nicoll, R. A.; Hays, F. A. TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists Science 2007, 318, 815-817 (Pubitemid 351411776)
31. Cruz, L. A.; Estebanez-Perpina, E.; Pfaff, S.; Borngraeber, S.; Bao, N.; Blethrow, J.; Fletterick, R. J.; England, P. M. 6-Azido-7-nitro-1,4- dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA receptor J. Med. Chem. 2008, 51, 5856-5860
32. Kasper, C.; Pickering, D. S.; Mirza, O.; Olsen, L.; Kristensen, A. S.; Greenwood, J. R.; Liljefors, T.; Schousboe, A.; Watjen, F.; Gajhede, M.; Sigurskjold, B. W.; Kastrup, J. S. The structure of a mixed GluR2 ligand-binding core dimer in complex with (S)-glutamate and the antagonist (S)-NS1209 J. Mol. Biol. 2006, 357, 1184-1201 (Pubitemid 43357980)
33. Robert, A.; Armstrong, N.; Gouaux, J. E.; Howe, J. R. AMPA receptor binding cleft mutations that alter affinity, efficacy, and recovery from desensitization J. Neurosci. 2005, 25, 3752-3762 (Pubitemid 40570408)