Azepinoindole derivatives with high affinity for brain dopamine and serotonin receptors

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 8, 1998, Pages 983-988

  Maryanoff, Bruce E ^a   McComsey, David F ^a   Martin, Gregory E ^a   Shank, Richard P ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,3,4,5 TETRAHYDRO 7,8 DIHYDROXY 1 METHYL 6 PHENYLTHIO 1H 3 BENZAZEPINE; AZEPINOINDOLE DERIVATIVE; DOPAMINE RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; INDOLE DERIVATIVE; NEUROLEPTIC AGENT; SEROTONIN RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; AVOIDANCE BEHAVIOR; BRAIN; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; NONHUMAN; RAT;

ANIMALS; ANTIPSYCHOTIC AGENTS; AZEPINES; BENZAZEPINES; BRAIN; DOPAMINE ANTAGONISTS; DRUG DESIGN; INDICATORS AND REAGENTS; INDOLES; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; RATS; RECEPTORS, DOPAMINE; RECEPTORS, DOPAMINE D1; RECEPTORS, DOPAMINE D2; RECEPTORS, SEROTONIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032554712     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00138-3     Document Type: Article

References (54)

1. 1. (a) Seeman, P.; van Tol, H. H. M. Trends Pharmacol. Sci. 1994, 15, 264.
2. (b) Sibley, D. R.; Monsma, F. J., Jr. Ibid. 1992, 13, 61.
3. (c) Sibley, D. R.; Monsma, F. J., Jr.; Shen, Y. Int. Rev. Neurobiol. 1993, 35, 391.
4. (d) Seeman, P. Neuropsychopharmacology 1992, 7, 261.
5. (e) Reynolds, G. Biochem. Soc. Trans. 1996, 24, 202.
6. (f) The Dopamine Receptors; Neve, K. A.; Neve, R. L., Eds.; Humana: Totowa, NJ, 1997, 553 pp.
7. 2. (a) Howard, H. R.; Seeger, T. F. Annu. Rept. Med. Chem. 1993, 28, 39.
8. (b) Reynolds, G. P. Trends Pharmacol. Sci. 1992, 13, 116.
9. (c) Tricklebank, M. D.; Bristow, L. J.; Hutson, P. H. Prog. Drug Res. 1992, 38, 299.
10. (d) Lowe, J. A. Curr. Med. Chem. 1994, 1, 50.
11. 3. (a) Schotte, A.; Janssen, P. F. M.; Megens, A. A. H. P.; Leysen, J. E. Brain Res. 1993, 631, 191.
12. (b) Schotte, A.; Janssen, P. F. M.; Gommeren, W.; Luyte, W. H. M. L.; Van Gompel, P.; Lesage, A. S.; De Loore, K.; Leysen, J. E. Psychopharmacology (Berlin) 1996, 124, 57.
13. 4. West, S. A.; Nemeroff, C. B. Drugs Today 1993, 29, 183.
14. 5. (a) Janssen, P. A. J.; Niemegeers, C. J. E.; Awouters, F.; Schellekens, K. H. L.; Megens, A. A. H. P.; Meert, T. F. J. Pharmacol. Exp. Ther. 1988, 244, 685.
15. (b) Leysen, J. E.; Gommeren, W.; Eens, A.; DeChaffoy DeCourcelles, D.; Stoof, J. C.; Janssen, P. A. J. Ibid. 1988, 247, 661.
16. 6. (a) Weinstock, J.; Heible, J. P.; Wilson, J. W., III Drug Future 1985, 10, 645.
17. (b) Barnett, A. Ibid. 1986, 11, 49.
18. (c) Pettersson, I.; Liljefors, T.; Bøgesø, K. J. Med. Chem. 1990, 33, 2197.
19. (d) Baindur, N.; Tran, M.; Niznik, H. B.; Seeman, P.; Neumeyer, J. L. Ibid. 1992, 35, 67.
20. 7. Kaiser, C.; Ali, F. E.; Bondinell, W. E.; Brenner, M.; Holden, K. G.; Ku, T. W.; Oh, H.-J.; Ross, S. T.; Yim, N. C. F.; Zirkle, C. L.; Hahn, R. A.; Sarau, H. M., Setler, P. E.; Wardell, J. R., Jr. J. Med. Chem. 1980, 23, 975.
21. 8. (a) Shank, R. P.; Gardocki, J. F.; Schneider, C. R.; Vaught, J. L.; Setler, P. E.; Maryanoff, B. E.; McComsey, D. F. J. Pharmacol. Exp. Ther. 1987, 242, 74.
22. (b) Martin, G. E.; Elgin, R. J., Jr.; Kesslick, J. M.; Baldy, W. J.; Mathiasen, J. R.; Shank, R. P.; Scott, M. K. Eur. J. Pharmacol. 1988, 156, 223.
23. 9. (a) Batcho, A. D.; Liemgruber, W. Org. Syntheses 1985, 63, 214.
24. (b) Clark, R. D.; Repke, D. B. Heterocycles 1984, 22, 195.
25. (c) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003.
26. 10. (a) Khan, M. A.; Polya, J. B. J. Chem. Soc. (C) 1970, 85.
27. (b) Khan, M. A.; Rocha, E. K. Chem. Pharm. Bull. 1977, 25, 3110.
28. 4 gave poor results.)
29. 12. (a) Maryanoff, B. E.; McComsey, D. F.; Nortey, S. O. J. Org. Chem. 1981, 46, 355.
30. (b) Maryanoff, B. E.; McComsey, D. F. Ibid. 1978, 43, 2733.
31. 13. (a) Troxler, F.; Harnish, A.; Bormann, G.; Seeman, F.; Szabo, L. Helv. Chim. Acta 1968, 51, 1616.
32. (b) Varma, R. S.; Kabalka, G. W. Syn. Commun. 1985, 15, 151.
33. 14. Entwistle, I. D.; Johnstone, R. A. W.; Povall, T. J. J. Chem. Soc., Perkin Trans. I 1975, 1300.
34. 15. (a) Yamamoto, T.; Kurata, Y. Can. J. Chem. 1983, 61, 86.
35. (b) Lindley, J. Tetrahedron 1984, 40, 1433.
36. (c) Paine, A. T. J. Am. Chem. Soc. 1987, 109, 1496.
37. 16. (a) Sirowej, H.; Khan, S. A.; Plieninger, H. Synthesis 1972, 84.
38. (b) Attempted arylation at other stages involving de-arylated intermediates corresponding to 13, 14, 15, or 16 failed miserably.
39. 17. McOmie, J. F. W.; Watts, M. L.; West, D. E. Tetrahedron 1968, 24, 2289.
40. 18. Chao, T. H.; Cipriani, L. P. J. Org. Chem. 1961, 26, 1079.
41. 19. (a) Gribble, G. W.; Leese, R. M.; Evans, B. E. Synthesis 1977, 172.
42. (b) Gribble, G. W.; Lord, P. D.; Skotnicki, J.; Dietz, S. E.; Eaton, J. T.; Johnson, J. L. J. Am. Chem. Soc. 1974, 96, 7812.
43. 20. (a) Maryanoff, B. E.; Vaught, J. L.; Shank, R. P.; McComsey, D. F.; Costanzo, M. J.; Nortey, S. O. J. Med. Chem. 1990, 33, 2793.
44. 50=0.30 (0.06-1.43) mg/kg].
45. 21. For a related l-aryl-3-(dimethylaminomethyl)indole with similar biological activity, see: Andersen, K.; Liljefors, T.; Hyttel, J.; Perregaard, J. J. Med. Chem. 1996, 39, 3723.
46. 22. (a) Indole 24 was reported previously (ref 22b and 22c), and Clark et al. (ref 22b) employed a similar Mannich cyclization.
47. (b) Clark, R. D.; Weinhardt, K. K.; Berger, J.; Fisher, L. E.; Brown, C. M.; MacKinnon, A. C.; Kilpatrick, A. T.; Spedding, M. J. Med. Chem. 1990, 33, 633.
48. (c) Heindl, J.; Schroeder, G. WO 87/00522, 1987 (Chem. Abstr. 1987, 106, 156272h).
49. 23. For other reports on conformationally constrained 3-benzazepines, see: (a) Weinstock, J.; Oh, H.-J.; DeBrosse, C. W.; Eggleston, D. S.; Wise, M.; Flaim, K. E.; Gessner, G. W.; Sawyer, J. L.; Kaiser, C. J. Med. Chem. 1987, 30, 1303.
50. (b) Berger, J. G.; Chang, W. K.; Clader, J. W.; Hou, D.; Chipkin, R. E.; McPhail, A. T. Ibid. 1989, 32, 1913.
51. (c) Ref 6c.
52. (d) Ref 22b.
53. 24. (a) Andersen, K.; Liljefors, T.; Gundertofte, K.; Perregaard, J.; Bøgesø, K. P. J. Med. Chem. 1994, 37, 950.
54. (b) Robertson, D. W.; Fuller, R. W. Annu. Rept. Med. Chem. 1988, 23, 49.