Synthesis, structure-activity relationships, and molecular modeling studies of N-(indol-3-ylglyoxylyl)benzylamine derivatives acting at the benzodiazepine receptor

Journal of Medicinal Chemistry

Volumn 39, Issue 26, 1996, Pages 5083-5091

  Da Settimo, Antonio ^a   Primofiore, Giampaolo ^a   Da Settimo, Federico ^a   Marini, Anna Maria ^a   Novellino, Ettore ^b   Greco, Giovanni ^b   Martini, Claudia ^a   Giannaccini, Gino ^a   Lucacchini, Antonio ^a  

^a UNIVERSITY OF PISA   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

BENZODIAZEPINE DERIVATIVE; BENZODIAZEPINE RECEPTOR; BENZYLAMINE DERIVATIVE; FLUNITRAZEPAM; TERT BUTYLBICYCLOPHOSPHOROTHIOATE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN MEMBRANE; CHLORIDE TRANSPORT; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG SYNTHESIS; HYPERPOLARIZATION; MOLECULAR MODEL; MOUSE; NEUROTRANSMITTER RELEASE; NONHUMAN; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BRAIN; CATTLE; INDOLES; MICE; MODELS, MOLECULAR; RADIOLIGAND ASSAY; RECEPTORS, GABA-A; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0030474838     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960240i     Document Type: Article

References (59)

1. A Receptor Channels. Annu. Rev. Neurosci. 1994, 17, 569-602.
2. 8 Ligands. Curr. Med. Chem. 1994, 3, 226-253.
3. Doble, A.; Martin, I. L. Multiple Benzodiazepine Receptors: No Reason for Anxiety. Trends Pharmacol. Sci. 1992, 13, 76-81.
4. Squires, R. F.; Braestrup, C. Benzodiazepine Receptors in Rat Brain. Nature 1977, 266, 732-734.
5. Mohler, H.; Okada, T. Benzodiazepine Receptors: Demonstration in the Central Nervous System. Science 1977, 198, 849-851.
6. Haefely, W. E.; Kyburz, E.; Gerecke, M.; Mohler, H. P. Recent Advances in the Molecular Pharmacology of Benzodiazepine Receptors and in the Structure-Activity Relationship of Their Agonist and Antagonist. Adv. Drug Res. 1985, 14, 166-322.
7. Villar, H. O.; Davies, M. F.; Loew, G. H.; Maguire, P. A. Molecular Models for Recognition and Activation at the Benzodiazepine Receptor: a Review. Life Sci. 1991, 48, 593-602.
8. Zhang, W.; Koehler, K. F.; Zhang, P.; Cook, J. M. Development of a Comprehensive Pharmacophore Model for the Benzodiazepine Receptor. Drug Des. Discovery 1995, 12, 193-248.
9. Lippke, K. P.; Schunack, W. G.; Wenning, W.; Müller, W. E. β-Carbolines as Benzodiazepine Receptor Ligands. 1. Synthesis and Benzodiazepine Receptor Interaction of Esters of β-Carboline-3-carboxylic Acid. J. Med. Chem. 1983, 26, 499-503.
10. Hagen, T. J.; Skolnick, P.; Cook, J. M. Syntheses of 6-Substituited β-Carbolines That Behave as Benzodiazepine Receptor Antagonists or Inverse Agonists. J. Med. Chem. 1987, 30, 750-753.
11. Allen, M. S.; Hagen, T. J.; Trudell, M. L.; Codding, P. W.; Skolnick, P.; Cook, J. M. Syntheses of Novel 3-Substituted β-Carbolines as Benzodiazepine Receptor Ligands: Probing the Benzodiazepine Receptor Pharmacophore. J. Med. Chem. 1988, 31, 1854-1861.
12. Yokoyama, N.; Ritter, B.; Neubert, A. D. 2-Arylpyrazolo-[4,3-c]quinolin-3-ones: Novel Agonist, Partial Agonist, and Antagonist of Benzodiazepines. J. Med. Chem. 1982, 25, 337-339.
13. Shindo, H.; Takada, S.; Murata, S.; Eigyo, M.; Matsushita, A. Thienylpyrazoloquinolines with High Affinity to Benzodiazepine Receptors: Continuous Shift from Inverse Agonist to Agonist Properties Depending on the Size of the Alkyl Substituent. J. Med. Chem. 1989, 32, 1213-1217.
14. Tarzia, G.; Occelli, E.; Toja, E.; Barone, D.; Corsicò, N.; Gallico, L.; Luzzani, F. 6-(Alkylamino)-3-aryl-1,2,4-triazolo[3,4-a]phthalazines. A New Class of Benzodiazepine Receptor Ligands. J. Med. Chem. 1988, 31, 115-1123.
15. Toja, E.; Tarzia, G.; Barone, D.; Luzzani, F.; Gallico, L. Benzodiazepine Receptor Binding and Anticonflict Activity in a Series of 3,6-Disubstituted Pyridazino[4,3-c]isoquinolines Devoid of Anticonvulsivant Properties. J. Med. Chem. 1985, 28, 1314-1319.
16. Gardner, C. R. Interpretation of the Behavioral Effects of Benzodiazepine Receptor Ligands. Drugs Future 1989, 14, 51-67.
17. Hoyer, D.; Boddeke, H. W. G. M. Partial Agonists, Full Agonists, Antagonists: Dilemmas of Definition. Trends Pharmacol. Sci. 1993, 14, 270-275.
18. Sternbach, L. H. In The Benzodiazepines: from Molecular Biology to Clinical Practice; Costa, E., Ed.; Raven: New York, 1983; pp 1-6.
19. Haefely, W.; Martin, J. R.; Schoch, P. Novel Anxiolytics That Act as Partial Agonist at Benzodiazepine Receptors. Trends Pharmacol. Sci. 1990, 11, 452-456.
20. Allen, M. S.; LaLoggia, A. J.; Dorn, L. J.; Martin, M. J.; Costantino, G.; Hagen, T.; Koehler, K. F.; Skolnick, P.; Cook, J. M. Predictive Binding of β-Carbolines Inverse Agonists and Antagonists via the CoMFA/GOLPE Approach. J. Med. Chem. 1992, 35, 4001-4010.
21. A Receptor Subtypes. Pharmacol. Rev. 1995, 47, 181-234
22. Klepner, C. A.; Lippa, A. S.; Benson, D. I.; Sano, M. C.; Beer, B. Resolution of Two Biochemically and Pharmacologically Distinct Benzodiazepine Receptors. Pharmacol. Biochem. Behav. 1979, 11, 457-462.
23. 3H-Benzodiazepine Binding Sites in Brain and of Benzodiazepine Pharmacological Properties. Pharmacol. Biochem. Behav. 1983, 18, 311-318.
24. Young, W. S., III; Niehoff, D.; Kuhar, M. J.; Beer, B.; Lippa, A. B. Multiple Benzodiazepine Receptor Localization by Light Microscopic Radiohistoehemistry. J. Pharmacol. Exp. Ther. 1981, 216, 434-439.
25. Richards, J. G.; Moehler, H. Benzodiazepine Receptors. Neuropharmacology 1984, 23, 233-242.
26. Bianucci, A. M.; Da Settimo, A.; Da Settimo, F.; Primofiore, G.; Martini, C.; Giannaccini, G.; Lucacchini, A. Benzodiazepine Receptor Affinity and Interaction of Some N-(Indol-3-ylglyoxylyl)amine Derivatives. J. Med. Chem. 1992, 35, 2214-2220.
27. Primofiore, G.; Marini, A. M.; Da Settimo, F.; Martini, C.; Bardellini, A.; Giannaccini, G.; Lucacchini, A. Specific Inhibition of Benzodiazepine Receptor Binding by Some N-(Indol-3-ylglyoxylyl)amino Acid Derivatives: Stereoselective Interactions. J. Med. Chem. 1989, 32, 2514-2518.
28. Braestrup, C.; Nielsen, M.; Honorè, T.; Jensen, L. H.; Petersen, E. M. Benzodiazepine Receptor Ligands With Positive and Negative Efficacy. Neuropharmacology 1983, 22, 1451-1457.
29. Braestrup, C.; Nielsen, M. Benzodiazepine Receptors. In Handbook of Psychopharmacology; Iversen, L. L., Iversen, S. D., Snyder, S. H., Eds.; Plenum Press: New York, 1983; Vol. 17, pp 285-384.
30. Fryer, R. I.; Rios, R.; Zhang, P.; Gu, Z. Q.; Wong, G.; Basile, A. S.; Skolnick, P. Structure Activity Relationships of 2-Phenylpyrazolo[4,3-c]quinolin-3-ones and Their N- and O-Methyl Analogs at Benzodiazepine Receptors. Med. Chem. Res. 1993, 3, 122-130.
31. 35S]-t-Butylbicyclophosphorothionate Binds with High Affinity to Brain-Specific Sites Coupled to γ-Aminobutyric Acid-A and Ion Recognition Sites. Mol. Pharmacol. 1983, 23, 326-336.
32. 35S]TBPS Binding to Purified Benzodiazepine-GABA-Ionophore Receptor Complex: the Effect of GABA on the Modulation Exerted by Benzodiazepine Site Ligands. Neurochem. Int. 1989, 15, 377-379.
33. - Uptake in Rat Cerebrocortical Membranes. Mol. Pharmacol. 1991, 39, 394-398.
34. Da Settimo, A.; Primofiore, G.; Marini, A. M.; Ferrarini, P. L.; Franzone, J. S.; Cirillo, R.; Reboani, M. C. N-(indol-3-ylglyoxylyl)-methionine Derivatives: Preparation and gastric Anti-Secretory Activity. Eur. J. Med. Chem. 1988, 23, 21-24.
35. Villar, H. O.; Uyeno, E. T.; Toll, L.; Polgar, W.; Davies, M. F.; Loew, G. H. Molecular Determinants of Benzodiazepine Receptor Affinities and Anticonvulsant Activities. Mol. Pharmacol. 1989, 36, 589-600.
36. Ananthan, S.; Clayton, S. D.; Ealick, S. E.; Wong, G.; Evoniuk, G. E.; Skolnick, P. Synthesis and Structure-Activity Relationships of 3,5-Disubstituted 4,5-Dihydro-6H-imidazo[1,5-a][1,4]-benzodiazepin-6-ones at Diazepam-Sensitive and Diazepam-Insensitive Benzodiazepine Receptors. J. Med. Chem. 1993, 36, 479-490.
37. A. Mol. Pharmacol. 1992, 42, 294-301.
38. A/Benzodiazepine Receptor. J. Med. Chem. 1994, 37, 758-768.
39. Hansch, C.; Leo, A.; Elkins, D. Partition Coefficients and their Use. Chem. Rev. 1971, 71, 525-616.
40. Hansch, C.; Björkroth, J. P.; Leo, A. Hydrophobicity and Central Nervous System Agents: On the Principle of Minimal Hydrophobicity in Drug Design. J. Pharm. Sci. 1987, 76, 663-687.
41. 3H]Flunitrazepam. Eur. J. Pharmacol. 1978, 48, 213-218.
42. Allen, M. S.; Tan, Y. C.; Trudell, M. L.; Narayanan, K.; Schindler, L. R.; Martin, M. J.; Schultz, C.; Hagen, T. J.; Koehler, K. F.; Codding, P. W.; Skolnick, P.; Cook, J. M. Synthetic and Computer-Assisted Analysis of the Pharmacophore for the Benzodiazepine Receptor Inverse Agonist Site. J. Med. Chem. 1990, 33, 2343-2357.
43. Diaz-Arauzo, H.; Koehler, K. F.; Hagen, T. J.; Cook, J. M. Synthetic and Computer Assisted Analysis of the Pharmacophore for Agonists at Benzodiazepine Receptors. Life Sci. 1991, 49, 207-216.
44. Zhang, W.; Cook, J. M. Novel Organic Reactions in the Search for Anxioselective Anxiolytics at the Benzodiazepine Receptor. In Drug Design for Neuroscience; Kozikowski, A., Ed.; Raven Press: New York, 1993; pp 87-117.
45. Szkaradzinska, M. B.; Roszak, A. W.; Trudell, M. L.; Cook, J. M.; Codding, P. W. Structure of 2-Chloro-7,12-dihydropyrido-[3,2-b:5,4-b′]diindole. Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1992, C48, 382-384.
46. 2O. Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1984, C40, 1981-1983.
47. 3O. Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1985, C41, 107-110.
48. Dewar, M. J.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AM1: A New General Purpose Quantum Mechanical Molecular Model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
49. Da Settimo, A.; Primofiore, G.; Da Settimo, F.; Marini, A. M.; Novellino, E.; Greco, G.; Martini, C.; Senatore, G.; Lucacchini, A. Synthesis of 3-(2′-furoyl)indole Derivatives as Potential New Ligands at the Benzodiazepine Receptor, Structurally More Restrained Analogues of Indoleglyoxylylamides. Farmaco 1995, 50, 311-320.
50. Martin, M. J.;Trudell, M. L.; Diaz-Arauzo, H.; Allen, M. S.; Deng, L.; Schultz, C. A.; Tan, Y.-C.; Bi, Y.; Narayanan, K.; Dorn, L. J.; Koehler, K. F.; Skolnick, P.; Cook, J. M. Molecular Yardsticks: Rigid Probes to Define the Spatial Dimensions of the Benzodiazepine Receptor Binding Site. J. Med. Chem. 1992, 35, 4105-4117.
51. Verloop, A.; Hoogenstraaten, W.; Tipker, J. Development and Application of New Steric Substituent Parameters in Drug Design. In Drug Design; Ariens, E. J., Ed.; Academic Press: New York, 1976; Vol. 7, pp 165-207.
52. SYBYL Molecular Modeling System (version 6.01), TRIPOS Assoc. St. Louis, MO.
53. MOPAC (version 5.00), Quantum Chemistry Program Exchange No. 455, 1989.
54. Allen, F. H.; Bellard, S.; Brice, M. D.; Cartwright, B. A.; Doubleday, A.; Higgs, H.; Hummelink, T.; Hummelink-Peters, B. G.; Kennard, O.; Motherwell, W. D. S.; Rodgers, J. R.; Watson, D. G. The Cambridge Crystallographic Data Centre: Computer-Based Search, Retrieval, Analysis and Display of Information. Acta Crystallogr. 1979, B35, 2331-2339.
55. Hoehne, E.; Seidel, I. The Molecular and Crystal Structure of p-Methylphenylglyoxylic Acid p-Chloroanilide. Krist. Tech. 1979, 14, 1097-1005.
56. Martini, C.; Lucacchini, A.; Ronca, G.; Hrelia, S.; Rossi, C. A. Isolation of Putative Benzodiazepine Receptors From Rat Brain Membranes by Affinity Chromatography. J. Neurochem. 1982, 38, 15-19.
57. Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. J. Protein Measurement With the Folin Phenol Reagent. J. Biol. Chem. 1951, 193, 265-275.
58. Trudell, M. L.; Lifer, S. L.; Tan, Y. C.; Martin, M. J.; Deng, L.; Skolnick, P.; Cook, J. M. Synthesis of Substituted 7,12-Dihydropyrido[3,2-b:5,4-b′]diindoles: Rigid Planar Benzodiazepine Ligands with Inverse Agonist/Antagonist Properties. J. Med. Chem. 1990, 33, 2412-2420.
59. Cain, M.; Weber, R. W.; Guzman, F.; Cook, J. M.; Barker, S. A.; Rice, K. C.; Crawley, J. N.; Paul, S. M.; Skolnick, P. β-Carbolines: Synthesis and Neurochemical and Pharmacological Actions on Brain Benzodiazepine Receptors. J. Med. Chem. 1982, 25, 1081-1091.