3,5-Dihydro-4H-2,3-benzodiazepine-4-thiones: A new class of AMPA receptor antagonists

Journal of Medicinal Chemistry

Volumn 41, Issue 18, 1998, Pages 3409-3416

  Chimirri, Alba ^a   De Sarro, Giovambattista ^b   De Sarro, Angela ^a   Gitto, Rosaria ^a   Quartarone, Silvana ^a   Zappalà, Maria ^a   Constanti, Andrew ^d   Libri, Vincenzo ^c,d  

^a UNIVERSITY OF MESSINA   (Italy)

^b UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^c UNIVERSITY OF ROME TOR VERGATA   (Italy)

^d UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 AMINOPHENYL) 4 METHYL 7,8 METHYLENEDIOXY 5H 2,3 BENZODIAZEPINE; 1 (4' AMINOPHENYL) 3,5 DIHYDRO 7,8 DIMETHOXY 4H 2,3 BENZODIAZEPINE 4 THIONE; AMPA RECEPTOR ANTAGONIST; BENZODIAZEPINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTICONVULSANT THERAPY; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; GUINEA PIG; MOUSE; NONHUMAN; SEIZURE;

ACOUSTIC STIMULATION; ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID; ANIMALS; ANTICONVULSANTS; BENZODIAZEPINES; CONVULSANTS; ELECTROSHOCK; EXCITATORY AMINO ACID AGONISTS; EXCITATORY AMINO ACID ANTAGONISTS; GUINEA PIGS; MALE; MICE; MICE, INBRED DBA; MOTOR ACTIVITY; OLFACTORY PATHWAYS; PATCH-CLAMP TECHNIQUES; PENTYLENETETRAZOLE; PYRROLIDINONES; RATS; RECEPTORS, AMPA; SEIZURES; STRUCTURE-ACTIVITY RELATIONSHIP; THIONES;

EID: 0032572821     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9800393     Document Type: Article

References (63)

1. De Sarro, G.; Chimirri, A.; De Sarro, A.; Gitto, R.; Grasso, S.; Giusti, P.; Chapman, A. G. GYKI 52466 and Related 2,3-Benzodiazepines as Anticonvulsant Agents in DBA/2 Mice. Eur. J. Pharmacol. 1995, 294, 411-422.
2. Chimirri, A.; De Sarro, G.; De Sarro, A.; Gitto, R.; Grasso, S.; Quartarone, S.; Zappalà, M.; Giusti, P.; Libri, V.; Constanti, A.; Chapman, A. G. 1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: Novel AMPA Receptor Antagonists. J. Med. Chem. 1997, 40, 1258-1269.
3. Monaghan, D. T., Wenthold, R. J., Eds.; The Ionotropic Glutamate Receptors; Humana Press: New Jersey, 1997.
4. Krogsgaard-Larsen, P.; Ebert, B.; Lund, T. M.; Bräuner-Osborne, H.; Sløk, F. A.; Johansen, T. N.; Brehm, L.; Madsen, U. Design of Excitatory Amino Acid Receptor Agonists, Partial Agonists and Antagonists: Ibotenic Acid as a Key Lead Structure. Eur. J. Med. Chem. 1996, 31, 515-537.
5. Lin, Z.; Kadaba, P. K. Molecular Targets for the Rational Design of Antiepileptic Drugs and Related Neuroprotective Agents. Med. Res. Rev. 1997, 17, 537-572.
6. (a) Ohmori, J.; Sakamoto, S.; Kubota, H.; Shimizu-Sasamata, M.; Okada, M.; Kawasaki, S.; Nikada, K.; Togami, J.; Furuya, T.; Murase, K. 6-(1H-Imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione Hydrochloride (YM90K) and Related Compounds: Structure-Activity Relationships for the AMPA-Type Non-NMDA Receptor. J. Med. Chem. 1994, 37, 467-475.
7. (b) Desos, P.; Lespagnol, J. M.; Morain, P.; Lestage, P.; Cordi, A. A. Structure-Activity Relationships in a Series of 2(1H)-Quinolones Bearing Different Acidic Function in the 3-Position: 6,7-Dichloro-2(1H)-oxoquinoline-3-phosphonic Acid, a New Potent and Selective AMPA/Kainate Antagonist with Neuroprotective Properties. J. Med. Chem. 1996, 39, 197-206.
8. (c) Honoré, T.; Davies, S. N.; Drejer, J.; Fletcher, E. J.; Jacobsen, P.; Lodge, D.; Nielsen, F. E. Quinoxalinediones: Potent Competitive non-NMDA Glutamate Receptor Antagonists. Science 1988, 241, 701-707.
9. 3H-CNQX Binds with Equal Affinity to two Agonist States of Quisqualate Receptor. Biochem. Pharmacol. 1989, 38, 3207-3212.
10. (e) Cai, S. X.; Huang, J. C.; Espitia, S. A.; Tran, M.; Ilyin, V. I.; Hawkinson. J. E.; Woodward, R. M.; Weber, E.; Keana, J. F. W. 5-(N-Oxyaza)-7-substituted-1,4-dihhydroquinoxaline-2,3-diones: Novel, Systemically Active and Broad Spectrum Antagonists for NMDA/glycine, AMPA and Kainate Receptors. J. Med. Chem. 1997, 40, 3679-3686.
11. De Sarro, G. B.; Ongini, E.; Bertorelli, R.; Aguglia, U.; De Sarro, A. Excitatory Amino Acid Neurotransmission through both NMDA and Non-NMDA Receptors is Involved in the Anticonvulsant Activity of Felbamate in DBA/2 Mice. Eur. J. Pharmacol. 1994, 262, 11-19.
12. Pelletier, J. C.; Hesson, D. P.; Jones, K. A.; Costa, A. M. Substituted 1,2-Dihydrophthalazines: Potent, Selective, and Noncompetitive Inhibitors of the AMPA Receptor. J. Med. Chem. 1996, 39, 343-346.
13. (a) Ornstein, P. L.; Arnold, M. B.; Augenstein, N. K.; Lodge, D.; Leander, J. D.; Schoepp, D. D. (3SR,4aRS,6RS,8aRS)-6-[2-(1H-Tetrazol-5-yl)ethyl]decahydro-isoquinoline-3- carboxylic Acid: A Structurally Novel, Systemically Active, Competitive AMPA Receptor Antagonist. J. Med. Chem. 1993, 36, 6, 2046-2048.
14. (b) Ornstein, P. L.; Arnold, M. B.; Allen, N. K.; Leander, J. D.; Tizzano, J. P.; Lodge, D.; Schoepp, D. D. (3SR,4aRS,6RS,8aRS)-6-(1H-Tetrazol-5-yl)decahydro-isoquinoline-3-carboxylic Acid, A Novel Competitive, Systemically Active NMDA and AMPA Receptor Antagonist. J. Med. Chem. 1995, 38, 4885-4890.
15. (a) Chapman, A. G.; Smith, S. E.; Meldrum, B. S. The Anticonvulsant Effect of the Non-NMDA Antagonists, NBQX and GYKI 52466 in Mice. Epilepsy Res. 1991, 9, 92-96.
16. (b) Smith, S. E.; Durmuller, N.; Meldrum, B. S. The non-N-methyl-D-aspartate Receptor Antagonists, GYKI 52466 and NBQX are Anticonvulsant in two Animal Models of Reflex Epilepsy. Eur. J. Pharmacol. 1991, 201, 179-183.
17. (c) Chapman, A. G.; Al-Zubaidy, Z.; Meldrum, B. S. Aniracetam Reverses the Anticonvulsant Action of NBQX and GYKI 52466 in DBA/2 Mice. Eur. J. Pharmacol. 1993, 231, 301-303.
18. (d) Donevan, S. D.; Rogawski, M. A. GYKI 52466, a 2,3-Benzodiazepine, is a Highly Selective, Noncompetitive Antagonist of AMPA/Kainate Receptor Responses. Neuron 1993, 10, 51-59.
19. (a) Rogawski, M. A. Therapeutic Potential of Excitatory Amino Acid Antagonists: Channel Blockers and 2,3-Benzodiazepines. Trends Pharmacol. Sci. 1993, 14, 325-331.
20. (b) Zorumski, C. F.; Yamada, K. A.; Price, M. D.; Olney J. W. Benzodiazepine Recognition Side Associated with non-NMDA Glutamate Receptor. Neuron 1993, 10, 61-67.
21. (c) Donevan, S. D.; Yamaguchi, S. I.; Rogawski, M. A. Non-N-methyl-D-aspartate Receptor Antagonism by 3-N-Substituted 2,3-Benzodiazepines: Relationship to Anticonvulsant Activity. J. Pharmacol. Exp. Ther. 1994, 271, 25-29.
22. (a) Lodge, D.; Bond, A.; Birds, D.; Palmer, A. J. Interaction between 2,3-Benzodiazepine and Cyclothiazide on the AMPA Subtype of Glutamate Receptor. Neurosci. Abs. 1993, 19, 124.4.
23. (b) Rammers, G.; Swandulla, D.; Collingridge, G. L.; Hartman, S.; Passons, C. G. Interaction of 2,3-Benzodiazepine and Cyclothiazide at AMPA Receptor: Patch Clamp Recordings in Cultured Neurones and Area CA1 in Hippocampal Slices. Br. J. Pharmacol. 1996, 117, 1209-1221.
24. (a) Lodge, D.; Bond, A.; O'Neill, M.; Hicks, C. A.; Jones, M. G. Stereoselective Effects of 2,3-Benzodiazepines In Vivo: Electrophysiology and Neuroprotection Studies. Neuropharmacology 1996, 35, 1681-1688.
25. (b) Bleakman, D.; Ballyk, B. A.; Schoepp, D. D.; Palmer, A. J.; Bath, C. P.; Sharpe, E. F.; Wooley, M. L.; Bufton, H. R.; Kamboj, R. K.; Tarnawa, I.; Lodge, D. Activity of 2,3-Benzodiazepines at Native Rat and Recombinant Human Glutamate Receptors In Vitro: Stereospecificity and Selectivity Profiles. Neuropharmacology 1996, 35, 1689-1702.
26. Tarnawa, I.; Farkas, S.; Berzsenyi, P.; Pataki, A.; Andrasi, F. Electrophysiological Studies with a 2,3-Benzodiazepine Muscle Relaxant: GYKI 52466. Eur. J. Pharmacol. 1989, 167, 193-199.
27. (a) Chimirri, A.; De Sarro, A.; De Sarro, G. B.; Grasso, S.; Trimarchi, G. R.; Zappalà, M. Synthesis and Anticonvulsant Properties of 2,3,3a,4-Tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones. J. Med. Chem. 1989, 32, 93-95.
28. (b) Chimirri, A.; Grasso, S.; Monforte, A. M.; Zappalà, M.; De Sarro, A.; De Sarro, G. B. Synthesis and Anticonvulsant Properties of 3-(1,3,4-Thiadiazol-2-yl)thiazolidin-4-ones. Farmaco 1991, 46, 935-943.
29. (c) De Sarro, A.; De Sarro, G. B.; Chimirri, A.; Grasso, S.; Monforte, A. M.; Zappalà, M. Anticonvulsant Activity of Pyrrolo[1′,2′:1,2]-imidazo[4,5-b]pyridines, Pyrrolo[2′,1′:2,3]imidazo[4,5-c]pyridines and Pyrrolo[2,1-f]purines in DBA/2 Mice. Gen. Pharmacol. 1994, 25, 1027-1031.
30. (a) De Sarro, G. B.; Zappalà, M.; Grasso, S.; Chimirri, A.; Spagnolo, C.; De Sarro, A. Molecular Requirement for Anticonvulsant Activity in a Series of 1,5-Benzodiazepines and [1,2,4]-Oxadiazolo[4,5-a][1,5]benzodiazepine Derivatives. Mol. Neuropharmacol. 1992, 1, 195-202.
31. (b) De Sarro, G.; Chimirri, A.; De Sarro, A.; Gitto, R.; Grasso, S.; Zappalà, M. 5H-[1,2,4]Oxadiazolo-[5,4-d][1,5]benzothiazepines as Anticonvulsant Agents in DBA/2 Mice. Eur. J. Med. Chem. 1995, 30, 925-929.
32. (a) De Sarro, G. B.; Zappalà, M.; Grasso, S.; Chimirri, A.; De Sarro, A. Molecular Requirement for Anticonvulsant Activity in a Series of Thiazolo-1,4-benzodiazepines and Comparison with Classical Benzodiazepines. Gen. Pharmacol. 1993, 24, 877-884.
33. (b) De Sarro, G. B.; Chimirri, A.; Zappalà, M.; Giusti, P.; Lipartiti, M.; De Sarro, A. Azirino[1,2-d][1,4]benzodiazepine Derivatives and Related 1,4-Benzodiazepines as Anticonvulsant Agents in DBA/2 Mice. Gen. Pharmacol. 1996, 27, 1155-1162.
34. (a) Chapman, A. G.; Croucher, M. J.; Meldrum, B. S. Evaluation of Anticonvulsant Drugs in DBA/2 Mice with Sound-Induced Seizures. Arzneim. -Forsch. 1984, 34, 1261-1264.
35. (b) Seyfried, T. N.; Glaser, G. H. A Review of Mouse Mutants as Genetic Models of Epilepsy. Epilepsia 1985, 26, 143-150.
36. (c) Engstrom, F. L.; Woodbury, D. M. Seizure Susceptibility in DBA/2 and C57 Mice: the Effects of Various Convulsants. Epilepsia 1988, 29, 389-395.
37. Ito, I.; Tanabe, S.; Kohda, A.; Sugiyama, H. Allosteric Potentiation of Quisqualate Receptors by Nootropic Drug Aniracetam. J. Physiol. (London) 1990, 424, 533-543.
38. (a) Chapman, A. G.; Meldrum, B. S. Noncompetitive N-methyl-D-aspartate Antagonists Protect Against Sound-Induced Seizures in DBA/2 Mice. Eur. J. Pharmacol. 1989, 166, 201-211.
39. (b) De Sarro, G. B.; De Sarro, A. Anticonvulsant Activity of Competitive Antagonists of NMDA Receptor in Genetically Epilepsy Prone Rats. Eur. J. Pharmacol. 1992, 215, 221-229.
40. (c) De Sarro, G. B.; De Sarro, A. Anticonvulsant Properties of Non-Competitive Antagonists of NMDA Receptor in Genetically Epilepsy Prone Rats. Comparison with CPPene. Neuropharmacology 1993, 32, 51-58.
41. (d) McEntee, W. C.; Crook, T. H. Glutamate, its Role in Learning, Memory, and the Aging Brain. Psychopharmacology 1993, 111, 391-401.
42. (e) Löscher, W. R.; Annies R.; Hönack, D. Comparison of Competitive and Uncompetitive NMDA Receptor Antagonist with Regard to Monoaminergic Neuronal Activity and Behavioural Effects in Rats. Eur. J. Pharmacol. 1993, 242, 263-274.
43. (a) Chiamulera, C.; Costa S.; Reggiani, A. Effect of NMDA- and Strychnine-Insensitive Glycine Site Antagonists on NMDA-Mediated Convulsions and Learning, Psychopharmacology 1990, 102, 551-552.
44. (b) Bliss, T. V. P.; Collingridge G. L. A Synaptic Model of Memory: Long-Term Potentiation in the Hippocampus. Nature 1993, 361, 31-39.
45. (c) Pasternain A. V.; Morales, M.; Lerma, J. Selective Antagonism of AMPA Receptors Unmasks Kainate Receptor-Mediate Responses in Hippocampal Neurones. Neuron 1995, 14, 185-189.
46. (a) Boyce, C. B. C.; Milborrow, B. V. A Simple Assessment of Partition Data for Correlating Structure and Biological Activity Using Thin-Layer Chromatography. Nature 1965, 208, 537-539.
47. (b) Pietrogrande, M. C.; Borea, P. A.; Biagi, G. L. Lipophilicity Measurements of Benzodiazepine-Receptor Ligands by Reversed-Phase Liquid Chromatography. Comparison between High-Performance Liquid and Thin-Layer Chromatography. J. Chromatogr. 1988, 447, 404-409.
48. (a) Hall, C. S. Genetic Differences in Fatal Audiogenic Seizures between two Inbred Strains of House Mice. J. Hered. 1947, 38, 2-6.
49. (b) Collins, R. L. Audiogenic Seizures. In Experimental Models of Epilepsy; Purpura, P., Penry, J. K, Tower, D., Woodbury, D. M., Walter, R., Eds.; Raven Press: New York, 1972; pp 347-372.
50. De Sarro, G. B.; Croucher, M. J.; Meldrum, B. S. Anticonvulsant Actions of DS 103-282: Pharmacological Studies in Rodents and the Baboon Papio papio. Neuropharmacology 1984, 23, 526-530.
51. Swinyard, E. A.; Brown, W. C.; Goodman, L. S. Comparative Assays of Antiepileptic in Mice and Rats. J. Pharmacol. Exp. Ther. 1952, 106, 319-330.
52. Swinyard, E. A.; Woodhead, J. M. Experimental Detection, Quantification and Evaluation of Anticonvulsants. In Epileptic Drugs; Woodbury, D. M., Penry, J. K., Pippenger, C. E., Eds.; Raven Press: New York, 1982; pp 111-126.
53. De Sarro, G. B.; Ongini, E.; Bertorelli, R.; Aguglia, U.; De Sarro, A. Excitatory Amino Acid Neurotransmission through both NMDA and Non-NMDA Receptors is Involved in the Anticonvulsant Activity of Felbamate in DBA/2 mice. Eur. J. Pharmacol. 1994, 262, 11-19.
54. (a) Apud, J. A.; Ito Y. Semi-preparative Purification of an Endogenous Ligand for Brain Serotonin-2-receptor by Coil Planet Centrifuge Counter-Current Chromatography. J. Chromatogr. 1991, 538, 177-185.
55. (b) Bylund, D. B.; Yamamura H. I. Methods for Receptor Binding. In Methods in Neurotransmitter Receptor Analysis; Yamamura, H. I., Enna, S. J., Kuhar, M. J., Eds.; Raven Press: New York, 1990; pp 1-35.
56. 3H]3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid to Rat Brain Membrane: a Selective High-Affinity Ligand for N-Methyl-D-aspartate Receptors J. Pharmacol. Exp. Ther. 1987, 240, 778-784.
57. 3H]-MK-801) in Rat Brain J. Pharmacol. Exp. Ther. 1991, 256, 811-819.
58. 3H]-(R,S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Binding Sites. J. Neurochem. 1990, 54, 686-695.
59. Dunham, N. W.; Miya, T. S. A Note on a Simple Apparatus for Detecting Neurological Deficit in Rats and Mice. J. Am. Pharm. Assoc. 1957, 46, 208-209.
60. Constanti, A.; Bagetta, G.; Libri, V. Persistent Muscarinic Excitation in Guinea-Pig Olfactory Cortex Neurons: Involvement of a Slow Post-Stimulus After Depolarizing Current. Neuroscience 1993, 56, 887-904.
61. Libri, V.; Constanti, A.; Calaminici, M.; Nisticò, G. A Comparison of the Muscarinic Response and Morphological Properties of Identified Cells in the Guinea-pig Olfactory Cortex in vitro. Neuroscience 1994, 59, 331-347.
62. Litchfield, J. T.; Wilcoxon, F. A Simplified Method of Evaluating Dose-Effects Experiments. J. Pharmacol. Exp. Ther. 1949, 96, 99-113.
63. McPherson, G. I. Ligand (release 2.0), Elsevier Biosoft, Cambridge, 1987.