Butyrophenone analogues in the carbazole series: Synthesis and determination of affinities at D2 and 5-HT(2A) receptors

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 24, 1998, Pages 3571-3576

  Masaguer, Christian F ^a   Formoso, Emilio ^a   Raviña, Enrique ^a   Tristán, Helena ^b   Loza, M Isabel ^b   Rivas, Emilia ^b   Fontenla, José Angel ^b  

^a UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^b Universidade de Santiago de Compostela   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

BUTYROPHENONE DERIVATIVE; CLOZAPINE; DOPAMINE 2 RECEPTOR; HALOPERIDOL; NEUROLEPTIC AGENT; QF 2001B; QF 2002B; QF 2003B; QF 2004B; QF 2006B; QF 2014B; SEROTONIN 2A RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; SCHIZOPHRENIA;

ANTIPSYCHOTIC AGENTS; BUTYROPHENONES; RECEPTOR, SEROTONIN, 5-HT2A; RECEPTORS, DOPAMINE D2; RECEPTORS, SEROTONIN;

MARTES PENNANTI;

EID: 0032535552     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00639-8     Document Type: Article

References (39)

1. 1. Martin, A. R. Antipsychotic Agents. In Burger's Medicinal Chemistry and Drug Discovery; Wolf, M. E., Ed. 5th. edition. Therapeutic Agents. Wiley Interscience, 1997; vol 5, p. 195.
2. 2. (a) Seemann, P. Synapse 1987, 192, 481-483;
3. (b) Sitsen, A. Current trends in antipsychotic agents. Script Report. PJB Publications: Richmond, U.K. 1990; p. 57.
4. 3. For a review of pharmacological properties and therapeutic uses of clozapine see Fitton, A.; Heel, R. C. Drugs 1990, 40, 722
5. 4. Ereshevsky, L.; Watanabe, N. D.; Trau-Johnson, T. K. Clin. Pharm. 1989, 8, 691.
6. 5. Ceulemans, D. L. S.; Gelders, Y. G.; Hoppenbrouwers, M. L.; Reyntjens, A. J. M.; Janssen, P. A. J. Psychopharmacology 1985, 85, 329.
7. 6. (a) Janssen, P. A. J.; Niemegeers, C. J. E.; Awouters, F.; Schellekens, K. H.; Megens, A. A. H. P.; Meert, T. F. J. J. Pharmacol. Exp. Ther. 1988, 244, 685-693;
8. (b) Leysen, J. E.; Gommeren, W.; Eens, A.; De Chaffoy de Courcelles, D.; Stoof, J. C.; Jansen, P. A. J. J. Pharmacol. Exp. Ther. 1988, 247, 661-670.
9. 7. (a) Meltzer, H. Y. ; Matsubara, S.; Lee, J. C. J. Pharmacol. Exp. Ther. 1989, 251, 238 ;
10. (b) Meltzer, H. C. ; Matsubara, S.; Lee, J. C. Psychopharmacol. Bull. 1989, 255, 390;
11. 2 Ratio Hypothesis. Curr. Med. Chem. 1994, 1, 50.
12. 8. Cortizo, L.; Santana, L.; Raviña, E.; Orallo, F.; Fontenla, J. A.; Castro, E.; de Ceballos, M. J. Med. Chem. 1991, 34, 2242-2247.
13. 9. Loza, I.; Verde, I.; Orallo, F.; Fontenla, J. A.; Calleja, J. M.; Raviña, E.; Cortizo, L.; de Ceballos, M. Bioorg. Med. Chem. Lett. 1991, 1, 717-720.
14. 10. Loza, I.; Ferreiro, T. G.; Sanz, F.; Lozoya, E.; Rodriguez, J.; Manaut, F.; Verde, I.; Castro, E.; Fontenla, J. A.; Cadavid, I.; Honrubia, M.; Fueyo, J.; Raviña, E. J. Pharm. Sci. 1993, 82, 513.
15. 11. Fontenla, J. A.; Osuna, J. A.; Rosa, E.; Castro, E.; Loza, I.; G-Ferreiro, T.; Calleja, J. M.; Sanz, F.; Rodriguez, J.; Fueyo, J.; Raviña, E.; Masaguer, C. F.; Vidal, A.; de Ceballos, M. J. Med. Chem. 1994, 37, 2564-2573.
16. 12. Raviña, E., Fueyo, J.; Masaguer, C. F.; Negreira, J.; Cid, J.; Loza, I.; Honrubia, H.; Tristan, H.; Ferreiro, T. G.; Fontenla, J. A.; Rosa, E.; Calleja, J. M.; de Ceballos, M. L. Chem. Pharm. Bull. 1996, 44, 534-541.
17. 13. Raviña, E.; Masaguer, C. F.; Cid, J.; Casariego, I.; Fontenla, J. A.; Ferreiro, T. G.; Cadavid, I.; Loza, I.; de Ceballos, M. L. Bioorg. Med. Chem. Lett. 1995, 5, 579-584.
18. 14. Masaguer, C. F.; Raviña, E. . Tetrahedron Lett. 1996, 37, 5171-5174.
19. 15. Masaguer, C. F.; Raviña, E.; Fontenla, J. A.; Loza, I. Bioorg. Med. Chem. Lett. 1997, 7, 913-918.
20. 16. Casariego I.; Masaguer, C. F.; Raviña, E.; Tetrahedron Lett. 1997, 31, 5555-5558.
21. 2C) Affinities. Sinthesis of Aminoalquil thienocycloalkanones as Putative Atypical Antipsychotics. J. Med. Chem. (submitted).
22. 18. Raviña, E.; Casariego. I.; Fontenla, J.A.; Loza, I. J. Med. Chem. (manuscript in preparation).
23. 19. Compound QF 0510B does not produce catalepsy at dose as high as 20 mg/Kg.
24. 20. (a) Boswell, R. F.; Welstead, W. J.; Duncan, R. C.; Funderburk, W. H. J. Med. Chem. 1978, 21, 136;
25. (b) Herndon, J. L.; Ismaiel, A.; Ingher, S. P.; Teitler, M.; Glennon, R. A. J. Med. Chem. 1992, 35, 4903.
26. 21. (a) Shustke, G. M.; Setescak, L. L.; Allen, R. C.; Davis, L.; Effland, R. E.; Ranbom, K.; Kitzen, J. M.; Wilker, J. C.; Novick, W. J. J. Med. Chem. 1982, 25, 36;
27. (b) Strupezewski, J. T.; Allen, R. C.; Gardenr, B. A.; Schmid, B. L.; Stache, U ; Glankowski, E. J.; Jones, M. C.; Ellis, D. B.; Huger, F. P.; Dunn, R. W. J. Med. Chem. 1985, 28, 761.
28. 22. (a) Kuehne, M. E.; Lambert, B. F. J. Am. Chem. Soc. 1959, 81, 4278-4287;
29. (b) Chapman, O. L.; Fitton, P. J. Am. Chem. Soc. 1963, 85, 41-47.
30. 23. For the Fischer indolization mechanism, see: Hughes, D. L.; Zhao, D. J. Org. Chem. 1993, 58, 228.
31. 24. The 4-(p-fluorobenzoyl)piperidine fragment may be considered as a butyrophenone moiety constrained in a six-membered ring. The importance of this fragment on CNS agents acting compounds is well known. See, among others, (a) Boswell, R. F., Jr.; Welstead, W. J., Jr.; Duncan, R. L., Jr.; Johnson, D. N.; Funderburk, W. H. J. Med. Chem. 1978, 21, 136-138;
32. (b) Herndon, J. L.; Ismaiel, A.; Ingher, S. P.; Teitler, M.; Glennon, R. A. J. Med. Chem. 1992, 35, 4903-4910;
33. (c) Ismaiel, A. M.; Arruda, K.; Teitler, M.; Glennon, R. A. J. Med. Chem. 1995, 38, 1196-1202.
34. 2A receptor interactions. A key structural feature that may play a prominent role in these interactions would be the benzylic carbonyl group. Ismaiel, A. M.; Arruda, K.; Teitler, M.; Glennon, R. A. J. Med. Chem. 1995, 38, 1196-1202.
35. 26. The bioisosteric relationships between benzoyl and 1,2-benzisoxazole moieties are notheworthy. See: (a) Shustke, G. M.; Setescak, L. L.; Allen, R. C.; Davis, L.; Effland, R. E.; Ranbom, K.; Kitzen, J. M.; Wilker, J. C.; Novick, W. J. J. Med. Chem. 1982, 25, 36-44;
36. (b) Strupezewski, J. T.; Allen, R.C.; Gardenr, B. A.; Schimid, B. L.; Stache, U.; Glankowzki, E. J.; Jones, M. C.; Ellis, D. B.; Huger, F. P.; Dunn, R. W. J. Med. Chem. 1985, 28, 761-769.
37. 2O: C, 76.02%; H, 8.51%; N, 9.85%. Found: C, 76.30%; H, 8.63%; N, 9.57%.
38. 13C-NMR, FTIR, MS). Yields given correspond to isolated pure compounds.
39. 29. Cheng, Y. C.; Prusoff. W. Biochem. Pharmacol. 1973, 22, 3099.