(S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid, a potent and selective agonist at the GluR5 subtype of ionotropic glutamate receptors. Synthesis, modeling, and molecular pharmacology

Journal of Medicinal Chemistry

Volumn 46, Issue 8, 2003, Pages 1350-1358

  Brehm, Lotte ^a   Greenwood, Jeremy R ^a   Hansen, Kasper B ^c   Nielsen, Birgitte ^a   Egebjerg, Jan ^c   Stensbøl, Tine B ^b   Bräuner Osborne, Hans ^a   Sløk, Frank A ^a   Kronborg, Tine T A ^a   Krogsgaard Larsen, Povl ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b H LUNDBECK A S   (Denmark)

^c AARHUS UNIVERSITY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3 (3 HYDROXY 7,8 DIHYDRO 6H CYCLOHEPTA[D]ISOXAZOL 4 YL)PROPIONIC ACID; 2 AMINO 3 (5 TERT BUTYL 3 HYDROXYISOTHIAZOL 4 YL)PROPIONIC ACID; ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; GLUTAMATE RECEPTOR; GLUTAMATE RECEPTOR 5; GLUTAMATE RECEPTOR ANTAGONIST; KAINIC ACID; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BINDING ASSAY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; IN VIVO STUDY; MOLECULAR MODEL; NONHUMAN; PROTEIN DOMAIN; PROTEIN EXPRESSION; RECEPTOR BLOCKING; STEREOISOMERISM;

ALANINE; AMINO ACID SEQUENCE; ANIMALS; CHO CELLS; CRICETINAE; EXCITATORY AMINO ACID AGONISTS; ISOXAZOLES; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR SEQUENCE DATA; MONTE CARLO METHOD; OOCYTES; PATCH-CLAMP TECHNIQUES; PROPIONIC ACIDS; RADIOLIGAND ASSAY; RECEPTORS, KAINIC ACID; SEQUENCE HOMOLOGY, AMINO ACID; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; XENOPUS LAEVIS;

EID: 0037431409     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0204441     Document Type: Article

References (58)

1. Excitatory Amino Acids and Synaptic Transmission; Wheal, H. V., Thomson, A. M., Eds.; Academic Press: London, 1995.
2. The Ionotropic Glutamate Receptors; Monaghan, D. T., Wenthold, R. J., Eds.; Humana Press: Totowa, NJ, 1997.
3. Parsons, C. G.; Danysz, W.; Quack, G. Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect. 1998, 11, 523-569.
4. The Metabotropic Glutamate Receptors; Conn, P. J., Patel, J., Eds.; Humana Press: Totowa, NJ, 1994.
5. Dingledine, R.; Borges, K.; Bowie, D.; Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 1999, 51, 7-61.
6. Bräuner-Osborne, H.; Egebjerg, J.; Nielsen, E. Ø.; Madsen, U.; Krogsgaard-Larsen, P. Ligands for glutamate receptors: design and therapeutic prospects. J. Med. Chem. 2000, 43, 2609-2645.
7. Knöpfel, T.; Kuhn, R.; Allgeier, H. Metabotropic glutamate receptors: novel targets for drug development. J. Med. Chem. 1995, 38, 1417-1426.
8. Monn, J. A.; Schoepp, D. D. Metabotropic glutamate receptor modulators: recent advances and therapeutic potential. Annu. Rep. Med. Chem. 2000, 35, 1-10.
9. Tanabe, Y.; Masu, M.; Ishii, T.; Shigemoto, R.; Nakanishi, S. A family of metabotropic glutamate receptors. Neuron 1992, 8, 169-179.
10. Aramori, I.; Nakanishi, S. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 1992, 8, 757-765.
11. Ionotropic Glutamate Receptors in the CNS; Jonas, P., Monyer, H., Eds.; Springer: Berlin, 1999.
12. Egebjerg, J.; Schousboe, A.; Krogsgaard-Larsen, P. Glutamate and GABA Receptors and Transporters. Structure, Function and Pharmacology; Taylor and Francis: London, 2002.
13. Hollmann, M.; Heinemann, S. Cloned glutamate receptors. Annu. Rev. Neurosci. 1994, 17, 31-108.
14. Dingledine, R.; Borges, K.; Bowie, D.; Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 1999, 51, 7-61.
15. Rosenmund, C.; Stern-Bach, Y.; Stevens, C. F. The tetrameric structure of a glutamate receptor channel. Science 1998, 280, 1596-1599.
16. Fletcher, E. J.; Lodge, D. New developments in the molecular pharmacology of α-amino-3-hydroxyisoxazole propionate and kainate receptors. Pharmocol. Ther. 1996, 70, 65-89.
17. Lees, G. J. Pharmacology of AMPA/kainate receptor ligands and their therapeutic potential in neurological and psychiatric disorders. Drugs 2000, 59, 33-78.
18. Lauridsen, J.; Honoré, T.; Krogsgaard-Larsen, P. Ibotenic acid analogues. Synthesis, molecular flexibility, and in vitro activity of agonists and antagonists at central glutamic acid receptors. J. Med. Chem. 1985, 28, 668-672.
19. Clarke, V. R. J.; Ballyk, B. A.; Hoo, K. H.; Mandelzys, A.; Pellizzari, A.; Bath, C. P.; Thomas, J.; Sharpe, E. F.; Davies, C. H.; Ornstein, P. L.; Shoepp, D. D.; Kamboj, R. K.; Collingridge, G. L.; Lodge, D.; Bleakman, D. A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature 1997, 389, 599-603.
20. 3H]ATPA: a high affinity ligand for GluR5 kainate receptors. Neuropharmacology 1999, 38, 1811-1817.
21. Stensbøl, T. B.; Johansen, T. N.; Egebjerg, J.; Madsen, U.; Ebert, B.; Krogsgaard-Larsen, P. Resolution, absolute stereochemistry and molecular pharmacology of the enantiomers of ATPA. Eur. J. Pharmacol. 1999, 380, 153-162.
22. Stensbøl, T. B.; Jensen, H. S.; Nielsen, B.; Johansen, T. N.; Egebjerg, J.; Frydenvang, K.; Krogsgaard-Larsen, P. Stereo-chemistry and molecular pharmacology of (S)-thio-ATPA, a new potent and selective GluR5 agonist. Eur. J. Pharmacol. 2001, 411, 245-253.
23. Thomas, N. K.; Hawkins, L. M.; Miller, J. C.; Troop, H. M.; Roberts, P. J.; Jane, D. E. Pharmacological differentiation of kainate receptors on neonatal rat spinal motoneurones and dorsal roots. Neuropharmacology 1998, 37, 1223-1237.
24. Chittajallu, R.; Braithwaite, S. P.; Clarke, V. R. J.; Henley, J. M. Kainate receptors: subunits, synaptic localization and function. Trends Pharmacol. Sci. 1999, 20, 26-35.
25. Krogsgaard-Larsen, P.; Nielsen, E. Ø; Curtis, D. R. Ibotenic acid analogues. Synthesis and biological and in vitro activity of conformationally restricted agonists at central excitatory amino acid receptors. J. Med. Chem. 1984, 27, 585-591.
26. Ebert, B.; Madsen, U.; Lund, T. M.; Holm, T.; Krogsgaard-Larsen, P. Molecular pharmacology of cortical and spinal AMPA receptors. Mol. Neuropharmacol. 1992, 2, 47-49.
27. Krogsgaard-Larsen, P.; Natova, L.; Christensen, S. B. Muscimol analogues. I. Syntheses of 4- and 8-aminocyclohepteno[1,2-d]-isoxazol-3-ols and 4-(3-aminopropyl)-5-methyl-3-isoxazolol. Acta Chem. Scand. 1977, 31, 577-583.
28. Ugi, I.; Offermann, K.; Herlinger, H.; Marquarding, D. Die Umsetzung von (S)-α-Phenyläthylamin und Isobutyraldehyd mit Benzoesäure und tert-Butyl-isocyanid als Modellreaktion für stereoselektive Peptid-Synthesen mittels Vierkomponenten-Kondensationen (The reaction of (S)-α-phenylethylamine and isobutyraldehyde with benzoic acid and tert-butyl isocyanide as a model reaction for stereoselective peptide synthesis through a four-component condensation). Leibigs Ann. Chem. 1967, 709, 1-10.
29. 6 subtype of metabotropic glutamic acid receptors. J. Med. Chem. 1997, 40, 3700-3705.
30. Dömling, A.; Ugi, I. Multicomponent reactions with isocyanides. Angew. Chem., Int. Ed. 2000, 39, 3168-3210.
31. Marquarding, D.; Hoffmann, P.; Heitzer, H.; Ugi, I. Stereoselective four-component condensations of α-ferrocenylethylamine and its absolute configuration. J. Am. Chem. Soc. 1970, 92, 1969-1971.
32. Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joullié, M. M. Total synthesis of (+)-furanomycin and stereoisomers. J. Am. Chem. Soc. 1980, 102, 7505-7510.
33. 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.
34. Shinbo, T.; Yamaguchi, T.; Nishimura, K.; Sugiura, M. Chromatographic separation of racemic amino acids by use of chiral crown ether-coated reversed-phase packings. J. Chromatogr. 1987, 405, 145-153.
35. Johansen, T. N.; Ebert, B.; Falch, E.; Krogsgaard-Larsen, P. AMPA receptor agonists: Resolution, configurational assignment and pharmacology of (+)-(S)- and (-)-(R)-2-amino-3-[3-hydroxy-5-(2-pyridyl)isoxazol-4-yl]propionic acid (2-Py-AMPA). Chirality 1997, 9, 274-280.
36. Falch, E.; Brehm, L.; Mikkelsen, I.; Johansen, T. N.; Skjærbæk, N.; Nielsen, B.; Stensbøl, T. B.; Ebert, B.; Krogsgaard-Larsen, P. Heteroaryl analogues of AMPA. 2. Synthesis, absolute stereochemistry, photochemistry, and structure - activity relationships. J. Med. Chem. 1998, 41, 2513-2523.
37. Johansen, T. N.; Ebert, B.; Bräuner-Osborne, H.; Didriksen, M.; Christensen, I. T.; Søby, K. K.; Madsen, U.; Krogsgaard-Larsen, P.; Brehm, L. Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid. J. Med. Chem. 1998, 41, 930-939.
38. Macromodel 7.2-8.0 (2001) and Glide 1.8 (2002); Schrödinger, Inc., 1500 SW First Avenue, Suite 1180, Portland, OR 97201.
39. Macromodel 7.2-8.0 (2001) and Glide 1.8 (2002); Schrödinger, Inc., 1500 SW First Avenue, Suite 1180, Portland, OR 97201.
40. Altschul, S. F.; Gish, W.; Miller, W.; Myers, E. W.; Lipman, D. J. Basic local alignment search tool (BLAST). J. Mol. Biol. 1990, 215, 403-410.
41. 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.
42. http://www.expasy.ch/swissmod/SWISS-MODEL.html. Schwede, T.; Diemand, A.; Guex, N.; Peitsch, M. C. Protein structure computing in the genomic era. Res. Microbiol. 2000, 151, 107-112.
43. 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.
44. Lunn, M.-L. Ph.D. Thesis, The Royal Danish School of Pharmacy, Copenhagen, Denmark, 2002.
45. Brehm, L.; Jørgensen, F. S.; Hansen, J. J.; Krogsgaard-Larsen, P. Agonists and antagonists for central glutamic acid receptors. Drug News Perspect. 1988, 1, 138-144.
46. Bräuner-Osborne, H.; Sløk, F. A.; Skjærbæk, N.; Ebert, B.; Sekiyama, N.; Nakanishi, S.; Krogsgaard-Larsen, P. A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid. J. Med. Chem. 1996, 39, 3188-3194.
47. Bräuner-Osborne, H.; Krogsgaard-Larsen, P. Pharmacology of (S)-homoquisqualic acid and (S)-2-amino-5-phosphonopentanoic acid [(S)-AP5] at cloned metabotropic glutamate receptors. Br. J. Pharmacol. 1998, 123, 269-274.
48. Bräuner-Osborne, H.; Nielsen, B.; Krogsgaard-Larsen, P. Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors. Eur. J. Pharmcol. 1998, 350, 311-316.
49. Lerma, J.; Paternain, A. V.; Rodríguez-Moreno, A.; López-García, J. C. Molecular physiology of kainate receptors. Physiol. Rev. 2001, 81, 971-998.
50. K5-containing kainate receptors prevent pilocarpine-induced limbic seizures. Nat. Neurosci. 2002, 5, 796-804.
51. Banke, T. G.; Greenwood, J. R.; Christensen, J. K.; Liljefors, T.; Schousboe, A.; Pickering, D. S. Identification of amino acid residues in GluR1 responsible for ligand binding and desensitisation. J. Neurosci. 2001, 21, 3052-3062.
52. Tanabe, Y.; Nomura, A.; Masu, M.; Shigemoto, R.; Mizuno, N.; Nakanishi, S. Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J. Neurosci. 1993, 13, 1372-1378.
53. 3H]MK-801 binding to the N-methyl-D-aspartate receptor ion channel complex by L-glutamate, glycine and polyamines. J. Neurochem. 1988, 51, 830-836.
54. Honoré, T.; Nielsen, M. Complex structure of quisqualate-sensitive glutamate receptors in rat cortex. Neurosci. Lett. 1985, 54, 27-32.
55. 3H]kainic acid receptor binding by divalent cations correlates with ion affinity for the calcium channel. Neuropharmacology 1987, 26, 1247-1251.
56. 3H]CGP 39653: a new N-methyl-D-aspartate antagonist radioligand with low nanomolar affinity in rat brain. Eur. J. Pharmacol. 1991, 192, 19-24.
57. Leatherbarrow, R. J. GraFit, version 3.0; Erithacus Software: Staines, U.K., 1992.
58. Christopoulus, A. Assessing the distrubution of parameters in models of ligand-receptor interactions: to log or not to log. Trends Pharmacol. Sci. 1998, 19, 351-357.