2-[N-acylamino(C1-C3)alkyl]indoles as MT1 melatonin receptor partial agonists, antagonists, and putative inverse agonists

Journal of Medicinal Chemistry

Volumn 41, Issue 19, 1998, Pages 3624-3634

  Spadoni, Gilberto ^a   Balsamini, Cesarino ^a   Bedini, Annalida ^a   Diamantini, Giuseppe ^a   Di Giacomo, Barbara ^a   Tontini, Andrea ^a   Tarzia, Giorgio ^a   Mor, Marco ^b   Plazzi, Pier Vincenzo ^b   Rivara, Silvia ^b   Nonno, Romolo ^c   Pannacci, Marilou ^c   Lucini, Valeria ^c   Fraschini, Franco ^c   Stankov, Bojidar Michaylov ^c  

^a UNIVERSITY OF URBINO   (Italy)

^b UNIVERSITY OF PARMA   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

INDOLE DERIVATIVE; MELATONIN DERIVATIVE; MELATONIN RECEPTOR; PARTIAL AGONIST;

ARTICLE; DRUG ACTIVITY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

3T3 CELLS; ANIMALS; GTP-BINDING PROTEINS; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); HUMANS; INDOLES; LIGANDS; MELATONIN; MICE; RATS; RECEPTORS, CELL SURFACE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, MELATONIN; SODIUM CHLORIDE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 14444284336     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970721h     Document Type: Article

References (85)

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. (c) Cassone, V. M. Effects of melatonin on vertebrate circadian systems. Trends Neurosci. 1990, 13, 457-464.
5. Cahill, G. M.; Besharse, J. C. Circadian rhythmicity in vertebrate retinas: regulation by a photoreceptor oscillator. In Progress in Retinal and Eye Research; Elsevier Science Ltd.: Great Britain, 1995; Vol. 14, pp 267-291.
6. Tamarkin, L.; Baird, C. J.; Almeida, O. F. X. Melatonin: a coordinating signal for mammalian reproduction? Science 1985, 227, 714-720.
7. 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.
8. 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. J. Neural. Transm. Suppl. 1986, 21, 257-267.
9. (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.
10. (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.
11. Sack, R. L.; Blood, M. L.; Lewy, A. J. Melatonin rhythms in night shift workers. Sleep 1992, 15, 434-441.
12. (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.
13. (b) Attenburrow, M. E. J.; Cowen, P. J.; Sharpley, A. L. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berlin) 1996, 126, 179-181.
14. Dollins, A. B.; Zhdanova, I. V.; Wurtman, R. J.; Lynch, H. J.; Deng, M. H. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 1824-1828.
15. 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.
16. (a) 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.
17. (b) Dubocovich, M. L.; Cardinali, D. P.; Hagan, R. M.; Krause, D. N.; Sudgen, D.; Vanhoutte, P. M.; Yocca, F. D. 1998 Melatonin receptors. The IUPHAR compendium of receptor characterization and classification; IUPHAR Media: London, in press.
18. Dubocovich, M. L. Melatonin receptors: are there multiple subtypes? Trends Pharmacol. Sci. 1995, 16, 50-56.
19. 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.
20. (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.
21. 1b melatonin receptor. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8734-8738.
22. (c) 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.
23. Liu, C.; Weaver, D. R.; Jin, X.; Shearman, L. P.; Pieschl, R. L.; Gribkoff, V. K.; Reppert, S. M. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 1997, 19, 91-102.
24. 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.
25. (a) Reiter, R. J.; Melchiorri, D.; Sewerynek, E.; Poeggeler, B.; Barlow-Walden, L.; Chuang, J. I.; Ortiz, G. G.; Acuna-Castroviejo, D. A review of the evidence supporting melatonin's role as an antioxidant. J. Pineal Res. 1995, 18, 1-11.
26. (b) 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.
27. Giusti, P.; Lipartiti, M.; Franceschini, D.; Schiavo, N.; Floreani, M.; Manev, H. Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. FASEB J. 1996, 10, 891-896.
28. (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.
29. (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.
30. (c) Bertuglia, S.; Marchiafava, P. L.; Colantuoni, A. Melatonin prevents ischemia reperfusion injury in hamster cheek pouch microcirculation. Cardiovasc. Res. 1996, 31, 947-952.
31. (a) Maestroni, G. J. M. The immunoneuroendocrine role of melatonin. J. Pineal Res. 1993, 14, 1-10.
32. (b) Lissoni, 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.
33. (c) Maestroni, G. 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.
34. (a) 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.
35. (b) Brzezinski, A. Melatonin in humans. N. Engl. J. Med. 1997, 336, 186-195.
36. (a) 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.
37. (b) Spadoni, G.; Stankov, B.; Duranti, A.; Biella, G.; Lucini, V.; Salvatori, A.; Fraschini, F. 2-substituted 5-methoxy-N-acyltryptamines: Synthesis, binding affinity for the melatonin receptor, and evaluation of the biological activity. J. Med. Chem. 1993, 36, 4069-4074.
38. (c) 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.
39. (d) 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.
40. 125I]Iodomelatonin binding sites. J. Med. Chem. 1995, 38, 2050-2060.
41. (f) 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.
42. (g) 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.
43. (a) Spadoni, G.; Balsamini, 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.
44. (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.
45. (c) 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.
46. (d) Sugden, D.; Chong, N. W. S.; Lewis, D. F. V. Structural requirements at the melatonin receptor. Br. J. Pharmacol. 1995, 114, 618-623.
47. (e) 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.
48. (f) 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.
49. (a) 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.
50. (b) Takaki, K. S.; Mahle, C. D.; Watson, A. J. Melatonergic ligands: pharmaceutical development and clinical applications. Curr. Pharm. Des. 1997, 3, 429-438.
51. Dubocovich, M. L. Luzindole (N-0774): a novel melatonin receptor antagonist. J. Pharmacol. Exp. Ther. 1988, 246, 902-910.
52. Copinga, S.; Van Brummelen, G.; Drijfhout, W. J.; Tepper, P. G.; Grol, C. J.; Horn, A. S.; Dubocovich, M. L. Synthesis and pharmacological evaluation of 4-aryl-2-amidotetralins: nonindolic melatonin-receptor agents. Proceedings of the XIIIth international symposium on medicinal chemistry, Paris, Sept 19-23, 1994.
53. 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.
54. Guardiola-Lemaitre, B.; Delagrange, P. Melatonin analogues: from pharmacology to clinical application. Eur. J. Med. Chem. 1995, 30, 643s-651s.
55. 1 presynaptic heteroreceptor. Naunyn-Schmiedeberg's Arch. Pharmacol. 1997, 355, 365-375.
56. 3H]dopamine release from retina. Eur. J. Pharmacol. 1984, 105, 193-194.
57. i = 10.3 and 6.5 nM) and that some of these compounds show a good propensity to behave as antagonists.
58. Davies, D. J.; Garratt, P. J.; Tocher, D. A.; Vonhoff, S.; Davies, J.; Teh, M. T.; Sugden, D. Mapping the melatonin receptor. 5. Melatonin agonists and antagonists derived from tetrahydrocyclopent[b]indoles, tetrahydrocarbazoles and hexahydrocyclohept-[b]indoles. J. Med. Chem. 1998, 41, 451-467.
59. 1a receptor following stable transfection into NIH3T3 cells. Br. J. Pharmacol. 1998, 124, 485-492.
60. 35
61. (a) Heward, C. B.; Hadley, M. E. Structure-activity relations of melatonin and related indolamines. Life Sci. 1975, 17, 1167-1177.
62. (b) Dubocovich, M. L. Characterization of a retinal melatonin receptor. J. Pharmacol. Exp. Ther. 1985, 234, 395-401.
63. 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.
64. Allen, M. S.; Hamaker, L. K.; La Loggia, A. J.; Cook, J. M. Entry into 6-methoxy-D(+)-tryptophans. Stereospecific synthesis of 1-benzenesulfonyl-6-methoxy-D(+)-tryptophan ethyl ester. Synth. Commun. 1992, 22, 2077-2102.
65. (a) Fanta, P. E. The Ullmann Synthesis of biaryls. Synthesis 1974, 9-21.
66. 2 binding site. 1. 3-(ω-Aminoalkyl)-1H-indoles. J. Med. Chem. 1995, 38, 1998-2008.
67. Siddappa, S.; Bhat, G. A. Synthesis of indole-2-carboxaldehydes, 2-(2-aminoethyl)- and 2-(2-aminopropyl)indoles. J. Chem. Soc., C. 1971, 178-81.
68. Wittig, G.; Schöllkopf, U. Triphenylphosphinemethylene as an olefin-forming reagent. I. Chem. Ber. 1954, 97, 1318-1330.
69. Novikov, S. S.; Shvekhgeimer, G. A. Preparation of aromatic nitro ketones and nitro nitriles by the Wittig reaction. Izvest. Akad. Nauk S.S.S.R., Otdel. Khim. Nauk 1960, 2061-2063; Chem. Abstr. 1961, 55, 13353g.
70. Novikov, S. S.; Shvekhgeimer, G. A. Preparation of aromatic nitro ketones and nitro nitriles by the Wittig reaction. Izvest. Akad. Nauk S.S.S.R., Otdel. Khim. Nauk 1960, 2061-2063; Chem. Abstr. 1961, 55, 13353g.
71. 50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
72. Morgan, P. J.; Barrett, P.; Howell, H. E.; Helliwell, R. Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem. Int. 1994, 24, 101-146.
73. 2-dopamine receptor of the anterior pituitary gland. Mol. Pharmacol. 1984, 26, 214-227.
74. Birnbaumer, L.; Abramowitz, J.; Brown, A. M. Receptor-effector coupling by G-proteins. Biochim. Biophys. Acta 1990, 1031, 163-224.
75. (a) Hilf, G.; Gierschik, P.; Jakobs, K. H. Muscarinic acetylcholine receptor-stimulated binding of guanosine 5′-O-(3-thiotriphosphate) to guanine nucleotide-binding proteins in cardiac membranes. Eur. J. Biochem. 1989, 186, 725-731.
76. 35S]thio)triphosphate binding. Mol. Pharmacol. 1993, 44, 115-123.
77. 4 receptors: antagonist studies. Br. J. Pharmacol. 1993, 109, 1120-1127.
78. Lew, M. J.; Angus, J. A. Analysis of competitive agonist-antagonist interactions by nonlinear regression. Trends Pharmacol. Sci. 1995, 16, 328-337.
79. Kubinyi, H. The Free-Wilson method and its relationship to the extrathermodynamic approach. In Comprehensive Medicinal Chemistry; Hansch, C., Sammes, P. G., Taylor, J. B., Eds.; Pergamon Press: Oxford, U.K., 1990; Vol. 4, pp 589-643.
80. Draper, N.; Smith, H. Applied Regression Analysis, 2nd ed.; Wiley: New York, 1981; pp 294-379.
81. Milligan, G.; Bond, R. A.; Lee, M. Inverse agonism: pharmacological curiosity or potential therapeutic strategy? Trends Pharmacol. Sci. 1995, 16, 10-13.
82. Hiremath, S. P.; Purohit, M. G. Synthesis of 3,4-dihydropyrido-[4,3-b]indoles using polyphosphate ester as a cyclizing agent. Indian J. Chem. 1972, 10, 984-986.
83. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248-254.
84. (a) Cozzi, B.; Stankov, B.; Viglietti-Panzica, C.; Capsoni, S.; Aste, N.; Lucini, V.; Fraschini, F.; Panzica, G. C. Distribution and characterization of melatonin receptors in the brain of the Japanese quail, Coturnix japonica. Neurosci. Lett. 1993, 150, 149-152.
85. (b) 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.