Melatonin receptor ligands: Synthesis of new melatonin derivatives and comprehensive comparative molecular field analysis (CoMFA) study

Journal of Medicinal Chemistry

Volumn 41, Issue 20, 1998, Pages 3831-3844

  Mor, Marco ^a   Rivara, Silvia ^a   Silva, Claudia ^a   Bordi, Fabrizio ^a   Plazzi, Pier Vincenzo ^a   Spadoni, Gilberto ^b   Diamantini, Giuseppe ^b   Balsamini, Cesarino ^b   Tarzia, Giorgio ^b   Fraschini, Franco ^c   Lucini, Valeria ^c   Nonno, Romolo ^c   Stankov, Bojidar Michaylov ^c  

^a UNIVERSITY OF PARMA   (Italy)

^b UNIVERSITY OF URBINO   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND; MELATONIN DERIVATIVE; MELATONIN RECEPTOR; N ACETYLSEROTONIN;

ARTICLE; CONFORMATION; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; LIGANDS; MELATONIN; MODELS, MOLECULAR; MOLECULAR CONFORMATION; QUAIL; RECEPTORS, CELL SURFACE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, MELATONIN; STRUCTURE-ACTIVITY RELATIONSHIP; SUPERIOR COLLICULUS;

EID: 15644374179     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9810093     Document Type: Article

References (84)

1. Reiter, R. J. Pineal Melatonin: Cell Biology of its Synthesis and of its Physiological Interactions. Endocr. Rev. 1991, 12, 151-180.
2. (a) Reiter, R. J. The Melatonin Rhythm: both a Clock and a Calendar. Experientia 1993, 49, 654-664.
3. (b) Underwood, H. The Pineal and Melatonin: Regulators of Circadian Function in Lower Vertebrates. Experientia 1990, 46, 120-128.
4. Cahill, G. M.; Besharse, J. C. Circadian Rhythmicity in Vertebrate Retinas: Regulation by a Photoreceptor Oscillator. Progress in Retinal Eye Research; Elsevier Science Ltd.: Great Britain, 1995; Vol. 14, pp 267-291.
5. Tamarkin, L.; Baird, C. J.; Alraeida, O. F. X. Melatonin: a Coordinating Signal for Mammalian Reproduction? Science 1985, 227, 714-720.
6. Oldani, A., Ferini-Strambi, L.; Zucconi, M.; Stankov, B.; Fraschini, F.; Smirne, S. Melatonin and Delayed Sleep Phase Syndrome: Ambulatory Polygraphic Evaluation. NeuroReport 1994, 6, 132-134.
7. Rosenthal, N. E.; Sack, D. A.; Jacobsen, F. M.; James, S. P.; Parry, B. L.; Arendt, J.; Tamarkin, L.; Wehr, T. A. Melatonin in Seasonal Affective Disorder and Phototherapy. Neural Transm. Suppl. 1986, 21, 257-267.
8. (a) Petrie, K.; Conaglen, J. V.; Thompson, L.; Chamberlain, K. Effect of Melatonin on Jet Lag after Long Haul Flights. Br. Med. J. 1989, 298, 705-707.
9. (b) Arendt, J.; Aldhous, M.; Marks, V. Alleviation of Jet Lag by Melatonin: Preliminary Results of a Controlled Double-Blind Trial. Annu. Rev. Chronopharmacol. 1986, 3, 49-52.
10. Sack, R. L.; Blood, M. L.; Lewy, A. J. Melatonin Rhythms in Night Shift Workers. Sleep 1992, 15, 434-441.
11. (a) Garfinkel, D.; Laudon, M.; Zisapel, N. Improvement of Sleep Quality by Controlled-Release Melatonin in Benzodiazepine-Treated Elderly Insomniacs. Arch. Gerontol. Geriatr. 1997, 24, 223-231.
12. (b) Sack, R. L.; Lewy, A. J.; Parrott, K.; Singer, C. M.; McArthur, A. J.; Blood, M. L.; Bauer, V. K. Melatonin Analogues and Circadian Sleep Disorders. Eur. J. Med. Chem. 1995, 30, 661-669s.
13. Zhdanova, I. V.; Wurtman, R. J.; Lynch, H. J.; Ives, J. R.; Dollins, A. B.; Morabito, C.; Matheson, J. K.; Schomer, D. L. Sleep-Inducing Effects of Low Doses of Melatonin Ingested in the Evening. Clin. Pharmacol. Ther. (St. Louis) 1995, 57, 552-558.
14. Morgan, P. J.; Lawson, W.; Davidson, G.; Howell, H. E. Guanine Nucleotides Regulate the Affinity of Melatonin Receptors on the Ovine Pars tuberalis. Neuroendocrinology 1989, 50, 359-362.
15. Reppert, S. M.; Weaver, D. R.; Godson, C. Melatonin Receptors Step into the Light: Cloning and Classification of Subtypes. Trends Pharmacol. Sci. 1996, 17, 100-102.
16. Ebisawa, T.; Karne, S.; Lerner, M. R.; Reppert, S. M. Expression Cloning of a High-Affinity Melatonin Receptor from Xenopus Dermal Melanophores. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 6133-6137.
17. (a) Reppert, S. M.; Weaver, D. R.; Ebisawa, T. Cloning and Characterization of a Mammalian Melatonin Receptor That Mediates Reproductive and Circadian Responses. Neuron 1994, 13, 1177-1185.
18. lb Melatonin Receptor. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8734-8738.
19. Mazzucchelli, C.; Pannacci, M.; Nonno, R.; Lucini, V.; Fraschini, F.; Stankov, B. M. The Melatonin Receptor in the Human Brain. Cloning Experiments and Distribution Studies. Mol. Brain Res. 1996, 39, 117-126.
20. (a) Maestroni, G. J. M. The Immunoneuroendocrine Role of Melatonin. J. Pineal Res. 1993, 14, 1-10.
21. (b) Lissom, P.; Barni, S.; Tancini, G.; Ardizzoia, A.; Cazzaniga, M.; Frigerio, F.; Brivio, F.; Conti, A.; Maestroni, G. J. M. Neuroimmunomodulation of Interleukin-2 Cancer Immunotherapy by Melatonin: Biological and Therapeutic Results. Adv. Pineal Res. 1994, 7, 183-189.
22. Maestroni, G. J. M.; Georges, J. M.; Hertens, E.; Galli, P.; Conti, A.; Pedrinis, E. Melatonin-Induced T-Helper Cell Hematopoietic Cytokines Resembling both Interleukin-4 and Dynorphin. J. Pineal Res. 1996, 21, 131-139.
23. Lissoni, P.; Paolorossi, F.; Tancini, G.; Ardizzoia, A.; Barni, S.; Brivio, F.; Maestroni, G. J. M.; Chilelli, M. A Phase II Study of Tamoxifen Plus Melatonin in Metastatic Solid Tumor Patients. Br. J. Cancer 1996, 74, 1466-1468.
24. Reiter, R. J. The Indoleamine Melatonin as a Free Radical Scavenger, Electron Donor, and Antioxidant: in Vitro and in Vivo Studies. Adv. Exp. Med. Biol. 1996, 398, 307-313.
25. Giusti, P.; Lipartiti, M.; Franceschini, D.; Schiavo, N.; Floreani, M.; Manev, H. Neuroprotection by Melatonin from Kainate-Induced Exitotoxicity in Rats. FASEB J. 1996, 10, 891-896.
26. Pozo, D.; Reiter, R. J.; Calvo, J. R.; Guerrero, J. M. Physiological Concentrations of Melatonin Inhibit Nitric Oxide Synthase in Rat Cerebellum. Life Sci. 1994, 55, 455-460.
27. (a) Lipartiti, M.; Franceschini, D.; Zanoni, R.; Gusella, M.; Giusti, P.; Cagnoli, C. M.; Kharlamov, A.; Manev, H. Neuroprotective Effects of Melatonin. Adv. Exp. Med. Biol. 1996, 398, 315-321.
28. (b) Manev, H.; Uz, T.; Kharlamov, A.; Joo, J. Y. Increased Brain Damage after Stroke or Excitotoxic Seizures in Melatonin-Deficient Rats. FASEB J. 1996, 10, 1546-1551.
29. Bertuglia, S.; Marchiafava, P. L.; Colantuoni, A. Melatonin Prevents Ischemia Reperfusion Injury in Hamster Cheek Pouch Micro-circulation. Cardiovasc. Res. 1996, 31, 947-952.
30. Takaki, K. S.; Mahle, C. D.; Watson A. J. Melatonergic Ligands: Pharmaceutical Development and Clinical Application. Curr. Pharm. Des. 1997, 3, 429-438.
31. 125I)-Iodomelatonin Binding Sites. J. Med. Chem. 1995, 38, 2050-2060.
32. (b) Depreux, P.; Lesieur, D.; Mansour, H. A.; Morgan, P.; Howell, H. E.; Renard, P.; Caignard, D. H.; Pfeiffer, B.; Delagrange, P.; Guardiola, B.; Yous, S.; Demarque, A.; Adam, G.; Andrieux, J. Synthesis and Structure-Activity Relationships of Novel Naphthalenic and Bioisosteric Related Amidic Derivatives as Melatonin Receptor Ligands. J. Med. Chem. 1994, 37, 3231-3239.
33. Yous, S.; Andrieux, J.; Howell, H. E.; Morgan, P. J.; Renard, P.; Pfeiffer, B.; Lesieur, D.; Guardiola-Lemaitre, B. Novel Naphthalenic Ligands with High Affinity for the Melatonin Receptor. J. Med. Chem. 1992, 35, 1484-1486.
34. Tarzia, G.; Diamantini, G.; Di Giacomo, B.; Spadoni, G.; Esposti, D.; Nonno, R.; Lucini, V.; Pannacci, M.; Fraschini, F.; Stankov, B. M. 1-(2-Alkanamidoethyl)-6-methoxyindole Derivatives: a New Class of Potent Indole Melatonin Analogues. J. Med. Chem. 1997, 40, 2003-2010.
35. Garratt, P. J.; Travard, S.; Vonhoff, S.; Tsotinis, A.; Sugden, D. Mapping the Melatonin Receptor. 4. Comparison of the Binding Affinities of a Series of Substituted Phenylalkyl Amides. J. Med. Chem 1996, 39, 1797-1805.
36. (a) Garratt, P. J.; Vonhoff, S.; Rowe, S. J.; Sugden, D. Mapping the Melatonin Receptor. 2. Synthesis and Biological Activity of Indole Derived Melatonin Analogues with Restricted Conformations of the C-3 Amidoethane Side Chain. Bioorg. Med. Chem. Lett. 1994, 4, 1559-1564.
37. (b) Spadoni, G.; Balsammi, C.; Diamantini, G.; Di Giacomo, B.; Tarzia, G.; Mor, M.; Plazzi, P. V.; Rivara, S.; Lucini, V.; Nonno, R.; Pannacci, M.; Fraschini, F.; Stankov, B. M. Conformationally Restrained Melatonin Analogues: Synthesis, Binding Affinity for the Melatonin Receptor, Evaluation of the Biological Activity, and Molecular Modeling Study. J. Med. Chem. 1997, 40, 1990-2002.
38. Copinga, S.; Tepper, P. G.; Grol, C. J.; Horn, A. S.; Dubocovich, M. L. 2-Amido-8-Methoxytetralins: A Series of Nonindolic Melatonin-Like Agents. J. Med. Chem. 1993, 36, 2891-2898.
39. Sugden, D. N-Acyl-3-amino-5-methoxychromans: a New Series of Non-Indolic Melatonin Analogues. Eur. J. Pharmacol. 1994, 254, 271-275
40. (e) Leclerc, V.; Depreux, P.; Lesieur, D.; Caignard, D. H.; Renard, P.; Delagrange, P.; Guardiola-Lemaitre, B.; Morgan, P. Synthesis and Biological Activity of Conformationally Restricted Tricyclic Analogues of the Hormone Melatonin. Bioorg. Med. Chem. Lett. 1996, 6, 1071-1076.
41. (f) Mathé-Allainmat, M.; Gaudy, F.; Sicsic, S.; Dangy-Caye, A. L.; Shuren, S.; Brémont, B.; Benatalah, Z.; Langlois, M.; Renard, P.; Delagrange, P. Synthesis of 2-Amido-2,3-Dihydro-1H-Phenalene Derivatives as New Conformationally Restricted Ligands for Melatonin Receptor. J. Med. Chem. 1996, 39, 3089-3095.
42. (g) Gruppen, G.; Grol, C. J. Synthesis of New Melatonin Agonists. 10th Camerino-Noordwijkerhout symposium: perspectives in receptor research (Camerino, Italy, September 10-14, 1995)
43. Sugden, D.; Chong, N. W. S.; Lewis, D. F. V. Structural Requirements at the Melatonin Receptor. Br. J. Pharmacol. 1995, 114, 618-623.
44. Spadoni, G.; Stankov, B.; Duranti, A.; Biella, G.; Lucini, V.; Salvatori, A.; Fraschini, F. 2-Substituted 5-Methoxy-N-Acyltryptemines: Synthesis. Binding Affinity for the Melatonin Receptor, and Evaluation of the Biological Activity. J. Med. Chem. 1993, 36, 4069-4074.
45. Martin, Y. C.; Bures, M. G.; Danaher, E. A.; De Lazzer, J.; Lico, I.; Pavlik, P. A. A Fast New Approach to Pharmacophore Mapping and its Application to Dopaminergic and Benzodiaz-epine Agonists. J. Comput.-Aided Mol. Des. 1993 7, 83-102.
46. Sicsic, S.; Serraz, I.; Andrieux, J.; Brémont, B.; Mathé-Allainmat, M.; Poncet, A.; Shen, S.; Langlois, M. Three-Dimensional Quantitative Structure-Activity Relationship of Melatonin Receptor Ligands: A Comparative Molecular Field Analysis Study. J. Med. Chem. 1997, 40, 739-748.
47. (a) Grol, C. J.; Jansen, J. M. The High Affinity Melatonin Binding Site Probed with Conformationally Restricted Ligands-II. Homology Modeling of the Receptor. Bioorg. Med. Chem. 1996, 4, 1333-1339.
48. (b) Jansen, J. M.; Copinga, S.; Gruppen, G.; Molinari, E. J.; Dubocovich, M. L.; Grol, C. J. The High Affinity Melatonin Binding Site Probed with Conformationally Restricted Ligands-I. Pharmacophore and Minireceptor Models. Bioorg. Med. Chem. 1996, 4, 1321-1332.
49. Reppert, S. M.; Weaver D. R.; Cassone V. M.; Godson, C.; Kolakowski, L. F., Jr. Melatonin Receptor are for the birds - Molecular Analysis of Two Receptor subtypes Differentially expressed in Chick brain. Neuron 1995, 15, 1003-1015.
50. Pickering, H.; Sword, S.; Vonhoff, S.; Jones, R.; Sugden D. Analogues of Diverse Structure are Unable to Differentiate Native Melatonin Receptors in the Chicken Retina, Sheep Pars tuberalis and Xenopus Melanophores. Br. J. Pharmacol 1996, 119, 379-387.
51. Navajas, C.; Kokkola, T.; Poso, A.; Honka, N.; Gynther, J.; Laitinen, J. T. A Rhodopsin-Based Model for Melatonin Recognition at its G Protein-Coupled Receptor. Eur. J. Pharmacol. 1996, 304, 173-183.
52. Cramer, R. D., III.; Patterson, D. E.; Bunce, J. D. Comparative Molecular Field Analysis (CoMFA). 1. Effect of Shape on Binding of Steroids to Carrier Proteins. J. Am. Chem. Soc. 1988, 110, 5959-5967.
53. Gaillard, P.; Carrupt, P.-A.; Testa, B.; Boudon, A. Molecular Lipophilicity Potential, a Tool in 3D QSAR: Method and Applications. J. Comput.-Aided Mol. Des. 1994, 8, 83-96.
54. SYBYL Molecular Modeling Software ver. 6.3, Tripos Inc., St. Louis (MO), USA.
55. Duranti, E.; Stankov, B.; Spadoni, G.; Duranti, A.; Lucini, V.; Capsoni, S.; Biella, G.; Fraschini, F. 2-Bromomelatonin: Synthesis and Characterization of a Potent Melatonin Agonist. Life Sci. 1992, 51, 479-485.
56. Still, I. W. J.; Strautmanis, J. R. Approaches to the Tetracyclic Eudistomins: the Synthesis of N(10)-Acetyleudistomin L. Can. J. Chem. 1990, 68, 1408-1419.
57. Yang, S. W.; Cordell, G. A. Metabolism Studies of Indole Derivatives Using a Staurosporine Producer, Streptomyces Staurosporeus. J. Nat. Prod. 1997, 60, 44-48.
58. Kennaway, D. J.; Hugel, H. M.; Clarke, S.; Tjandra, A.; Johnson, D. W.; Royles, P.; Webb, H. A.; Carbone, F. Structure-Activity Studies of Melatonin Analogues in Prepubertal Male Rats. Aust. J. Biol. Sci. 1988, 41, 393-400.
59. Velluz, L.; Muller, G.; Joly, R.; Nomine, G.; Mathieu, J.; Allais, A.; Warnant, J.; Valls, J.; Bucourt, R.; Jolly, J. Synthesis of Reserpine and New Derivatives of Yohimban. Bull. Soc. Chim. Fr. 1958, 673-677.
60. Yamada, F.; Saida, Y.; Somei, M. Structural Determination of a Natural Alkaloid, 5-Methoxy-1-oxo-1,2,3,4-tetrahydro-β-carboline and the Synthesis of the Corresponding 8-Methoxy Compound. Heterocycles 1986, 24, 2619-2627.
61. Crohare, R.; Merkuza, V. M.; Gonzalez, H. A.; Ruveda, E. A. 5,7-Dimethoxyindole and Related Compounds. J. Heterocycl. Chem. 1970, 7, 729-732.
62. Buzas, A.; Herisson, C.; Lavielle, G. Application of the Wittig-Horner Reaction to Indolinones. A Convenient Synthesis of Tryptamines. Synthesis 1977, 129-130.
63. (42) Suvorov, N. N.; Gordeev, E. N.; Vasin, M. V. Indole derivatives. CI. Synthesis and Biological Activity of Some Tryptamines. Khim. Geterotsikl. Soedin. 1974, 11, 1496-1501. [Chem. Abstr. 1975, 82, 139888g].
64. Suvorov, N. N.; Gordeev, E. N.; Vasin, M. V. Indole derivatives. CI. Synthesis and Biological Activity of Some Tryptamines. Khim. Geterotsikl. Soedin. 1974, 11, 1496-1501. [Chem. Abstr. 1975, 82, 139888g].
65. Hino, T.; Lai, Z.; Seki, H.; Hara, R.; Kuramochi, T.; Nakagawa, M. 1-(1-Pyrrolin-2-yl)-β-carbolines. Synthesis of Eudistomins H, I, and P. Chem. Pharm. Bull. 1989, 37, 2596-2600.
66. Spath, E.; Lederer, E. Synthese der Harmala-Alkaloide: Harmalin, Harmin und Harman. Ber. 1930, 63B, 120-125.
67. Frohn, M. A.; Seaborn, C. J.; Johnson, D. W.; Phillipou, G.; Seamark, R. F.; Matthews, C. D. Structure-Activity Relationship of Melatonin Analogues. Life Sci. 1980, 27, 2043-2046.
68. Cozzi, B.; Stankov, B.; Viglietti-Panzica, C.; Capsoni, S.; Aste, N.; Lucini, V.; Fraschini, F.; Panzica, G. C. Distribution and Characterization of Melatonin Receptor in the Brain of the Japanese Quail, Coturnix Japonica. Neurosci. Lett. 1993, 150, 149-152.
69. Stankov, B.; Cozzi, B.; Lucini, V.; Fumagalli, P.; Scaglione, F.; Fraschini, F. Characterization and Mapping of Melatonin Receptors in the Brain of Three Mammalian Species: Rabbit, Horse and Sheep. A Comparative in Vitro Binding Study. Neuroendocrinology 1991, 53, 214-221.
70. 125I]-Iodomelatonin Binding Sites in Chicken Brain and Sheep Pars tuberalis. Brain Res. 1991, 539, 151-154.
71. Copinga, S. The Semirigid 2-Aminotetralin System: A Structural Base for Dopamine- and Melatonin-Receptor Agents. Thesis defended at the State University of Groningen, The Netherlands, Faculty of Science, October 1994.
72. Schaper, K.-J. QSAR Analysis of Chiral Compounds Including Racemates. In Progress in clinical and biological research. QSAR: Quantitative Structure-Activity Relationships in Drug Design, vol. 291; Fauchère, J. L., Ed.; Alan R. Liss, Inc.: New York, 1989; pp 41-44.
73. Garratt, P. J.; Jones, R.; Tocher, D. A.; Sugden, D. Mapping the Melatonin Receptor. 3. Design and Synthesis of Melatonin Agonists and Antagonists Derived from 2-Phenyltryptamines. J. Med. Chem. 1995, 38, 1132-1139.
74. Garratt, P. J.; Jones, R.; Rowe, S. J.; Sugden, D. Mapping the Melatonin Receptor. 1. The 5-Methoxyl Group of Melatonin Is Not an Essential Requirement for Biological Activity. Bioorg. Med. Chem. Lett. 1994, 4, 1555-1558.
75. (a) SYBYL 6.3 Force Field Manual, p 234, Tripos Inc., St. Louis, MO.
76. (b) Clark, M.; Cramer, R. D., III.; Van Opdenbosch, N. Validation of the General Purpose Tripos 5.2 Force Field. J. Comput. Chem. 1989, 10, 982-1012.
77. Powell, M. J. D. Restart Procedures for the Conjugate Gradient Methodol. Mathematical Programming 1977, 12, 241-254.
78. SYBYL 6.3 Force Field Manual, p 290, Tripos Inc., St Louis, MO.
79. SYBYL 6.3 Ligand-Based Design Manual; Tripos Inc., St. Louis, MO; pp 215-236.
80. Cramer, R. D., III.; DePriest, S. A.; Patterson, D. E.; Hecht, P. The Developing Practice of Comparative Molecular Field Analysis. In 3D QSAR in Drug Design. Theory Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, 1993; p 456.
81. Wold, S.; Ruhe, A.; Wold, H.; Dunn, W. J. The Covariance Problem in Linear Regression. The Partial Least Squares (PLS) Approach to Generalized Inverses. SIAM J. Sci. Stat. Comput. 1984, 5, 735-743.
82. Cramer, R. D., III.; Bunce, J. D.; Patterson, D. E. Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR Studies. Quantum Struct.-Act. Relat. 1988, 7, 18-25.
83. Dubocovich, M. L. Melatonin Receptors: Are There Multiple Subtypes? Trends Pharmacol. Sci. 1995, 16, 50-56.
84. Cruciani, G.; Clementi, S., Baroni, M. Variable Selection in PLS Analysis. In 3D QSAR in Drug Design. Theory Methods and Applications; Kubinyi, H., Ed.; ESCOM: Leiden, 1993; p 552.