Benzimidazole derivatives. Part 5: Design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT 1A/5-HT 3 ligands

Bioorganic and Medicinal Chemistry

Volumn 12, Issue 19, 2004, Pages 5181-5191

  López Rodríguez, María L ^a   Benhamú, Bellinda ^a   Morcillo, Ma José ^b   Tejada, Ignacio ^a   Avila, David ^a   Marco, Isabel ^a   Schiapparelli, Lucio ^c   Frechilla, Diana ^c   Del Río, Joaquín ^c  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b UNIVERSIDAD NACIONAL DE EDUCACIÓN A DISTANCIA   (Spain)

^c UNIVERSITY OF NAVARRA   (Spain)

Author keywords

5 HT 1A receptor; 5 HT 3 receptor; Arylpiperazines; Benzimidazole derivatives; Cognitive dysfunction; Serotonin ligands

Indexed keywords

ALPHA 1A ADRENERGIC RECEPTOR; BENZIMIDAZOLE DERIVATIVE; DOPAMINE 2 RECEPTOR; MUSCARINIC RECEPTOR; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [(4 PHENYLPIPERAZIN 1 YL)METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [4 [3 (CHLOROPHENYL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (2 ETHOXYPHENYL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (2 ISOBUTOXYPHENYL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (2 ISOPROPOXYPHENYL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (2 PROPOXYPHENYL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (2,3 DIHYDRO 1,4 BENZODIOXAN 5 YL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (BENZIMIDAZOL 4 YL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 (NAPHTH 1 YL)PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; N (1 AZABICYCLO[2.2.2]OCT 3 YL) 2 [[4 [3 (TRIFLUOROMETHYL)PHENYL]PIPERAZIN 1 YL]METHYL]BENZIMIDAZOLE 4 CARBOXAMIDE; PIPERAZINE DERIVATIVE; SEROTONIN 1A RECEPTOR; SEROTONIN 3 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; COGNITIVE DEFECT; CONTROLLED STUDY; DRUG DESIGN; DRUG EFFECT; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HYPOTHERMIA; LEARNING TEST; MALE; MOUSE; NONHUMAN; PASSIVE AVOIDANCE; RAT;

ANIMALS; AVOIDANCE LEARNING; BENZIMIDAZOLES; COGNITION DISORDERS; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); GUINEA PIGS; HIPPOCAMPUS; HYPOTHERMIA; LIGANDS; MALE; MICE; MUSCLE CONTRACTION; PIPERAZINES; RATS; RATS, WISTAR; RECEPTOR, SEROTONIN, 5-HT1A; RECEPTORS, SEROTONIN, 5-HT3; SEROTONIN ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 4444372176     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2004.07.023     Document Type: Article

References (50)

1. H.G. Baumgarten, and M. Göthert Serotoninergic Neurons and 5-HT Receptors in the CNS Handbook of Experimental Pharmacology Vol. 129 1997 Springer-Verlag Berlin
2. G.R. Martin R.M. Eglen D. Hoyer M.W. Hamblin F. Yocca Advances in Serotonin Receptor Research: Molecular Biology, Signal Transmission, and Therapeutics 1998 Annals of the New York Academy of Sciences New York
3. N.M. Barnes, and T. Sharp Neuropharmacology 38 1999 1083
4. D. Hoyer, J.P. Hannon, and G.R. Martin Pharmacol. Biochem. Behav. 71 2002 533
5. L. Uphouse Neurosci. Biobehav. Rev. 21 1997 679
6. P.R. Saxena, P. De Vries, and C.M. Villalón Trends Pharmacol. Sci. 19 1998 311
7. J.A. Bikker, S. Trump-Kallmeyer, and S. Humblet J. Med. Chem. 41 1998 2911
8. P.J. Schwartz, E.H. Turner, D. Garcí-a-Borreguero, J. Sedway, R.G. Vetticad, T.A. Wehr, D.L. Murphy, and N.E. Rosenthal Psychiatry Res. 86 1999 9
9. Z. Sarnyai, E.L. Sibille, C. Pavlides, R.J. Fenster, B.S. McEwen, and M. Toth Proc. Nat. Acad. Sci. U.S.A. 97 2000 14731
10. J.L. Peglion, B. Goument, N. Despaux, V. Charlot, H. Giraud, C. Nisole, A. Newman-Tancredi, A. Dekeyne, M. Bertrand, P. Genissel, and M.J. Millan J. Med. Chem. 45 2002 165
11. F. Yasuno, T. Suhara, T. Nakayama, T. Ichimiya, Y. Okubo, A. Takano, T. Ando, M. Inoue, J. Maeda, and K. Suzuki Am. J. Psychiatry 160 2003 334
12. C. Veyrat-Follet, R. Farinotti, and J.L. Palmer Drugs 53 1997 206
13. J. Watters, M. Riley, I. Pedley, A. Whitehead, M. Overend, I. Goss, and V. Allgar Clin. Oncol. 13 2001 422
14. A.J. Greenshaw, and P.H. Silverstone Drugs 53 1997 20
15. F.E. Bloom, and M. Morales Neurochem. Res. 23 1998 653
16. Z.J. Zhang, D.E. Schmidt, T. de-Paulis, B.L. Trivedi, E.S. Onaivi, M.H. Ebert, and W.A. Hewlett Pharmacol. Biochem. Behav. 69 2001 571
17. M.L. López-Rodrí-guez, M.L. Rosado, B. Benhamú, M.J. Morcillo, A.M. Sanz, L. Orensanz, M.E. Beneitez, J.A. Fuentes, and J. Manzanares J. Med. Chem. 39 1996 4439
18. M.L. López-Rodrí-guez, M.J. Morcillo, E. Fernández, E. Porras, M. Murcia, A.M. Sanz, and L. Orensanz J. Med. Chem. 40 1997 2653
19. M.L. López-Rodrí-guez, M.J. Morcillo, T.K. Rovat, E. Fernández, B. Vicente, A.M. Sanz, M. Hernández, and L. Orensanz J. Med. Chem. 42 1999 36
20. M.L. López-Rodrí-guez, A. Viso, B. Benhamú, J.L. Rominguera, and M. Murcia Bioorg. Med. Chem. Lett. 9 1999 2339
21. M.L. López-Rodrí-guez, M.J. Morcillo, E. Fernández, E. Porras, L. Orensanz, M.E. Beneytez, J. Manzanares, and J.A. Fuentes J. Med. Chem. 44 2001 186
22. M.L. López-Rodrí-guez, M.L. Rosado, B. Benhamú, M.J. Morcillo, E. Fernández, and K.-J. Schaper J. Med. Chem. 40 1997 1648
23. M.L. López-Rodrí-guez, M.J. Morcillo, E. Fernández, M.L. Rosado, L. Pardo, and K.-J. Schaper J. Med. Chem. 44 2001 198
24. M.L. López-Rodrí-guez, B. Vicente, X. Deupi, S. Barrondo, M. Olivella, M.J. Morcillo, B. Benhamú, J.A. Ballesteros, J. Sallés, and L. Pardo Mol. Pharmacol. 62 2002 15
25. M.L. López-Rodrí-guez, M.J. Morcillo, E. Fernández, B. Benhamú, I. Tejada, D. Ayala, A. Viso, M. Olivella, L. Pardo, M. Delgado, J. Manzanares, and J.A. Fuentes Bioorg. Med. Chem. Lett. 13 2003 1429
26. M.L. López-Rodrí-guez, B. Benhamú, M.J. Morcillo, I.D. Tejada, L. Orensanz, M.J. Alfaro, and M.I. Martin J. Med. Chem. 42 1999 5020
27. D. Pascual, R. Girón, A. Alsasua, B. Benhamú, M.L. López-Rodrí-guez, and M.I. Martí-n Eur. J. Pharmacol. 462 2003 99
28. M.L. López-Rodrí-guez, B. Benhamú, M.J. Morcillo, I. Tejada, D. Avila, I. Marco, L. Schiapparelli, D. Frechilla, and J. Del Rí-o Bioorg. Med. Chem. Lett. 13 2003 3177
29. M.F. Hibert, I. McDermott, D.N. Middlemiss, A.K. Mir, and J.R. Fozard Eur. J. Med. Chem. 24 1989 31
30. M.L. López-Rodrí-guez, M.J. Morcillo, B. Benhamú, and M.L. Rosado J. Comput.-Aided Mol. Des. 11 1997 589
31. M.L. López-Rodrí-guez, D. Ayala, B. Benhamú, M.J. Morcillo, and A. Viso Curr. Med. Chem. 9 2002 443
32. G.M. Goodwin, R.J. De Souza, and A.R. Green Neuropharmacology 24 1985 1187
33. J. De Vry Psychopharmacology 121 1995 1
34. J. Roca, I. Artaiz, and J. Del RÃ-o Expert Opin. Investig. Drugs 4 1995 333
35. J.B. Jones, and K.E. Taylor Can. J. Chem. 55 1977 1653
36. G.E. Martin, R.J. Elgin, J.R. Mathiasen, C.B. Davis, J.M. Kesslick, W.J. Baldy, R.P. Shank, D.L. DiStefano, C.L. Fedde, and M.K. Scott J. Med. Chem. 32 1989 1052
37. Parcell, R. F. U.S. 2,922,788, 1960; Chem. Abstr. 1969, 71, 91527g
38. J.L. Peglion, H. Canton, K. Bervoets, V. Audinot, M. Brocco, A. Gobert, S. Le MarouilleGirardon, and M.J. Millan J. Med. Chem. 38 1995 4044
39. M. Nishiyama, T. Yamamoto, and Y. Koie Tetrahedron Lett. 39 1998 617
40. M.L. López-Rodrí-guez, B. Benhamú, D. Ayala, J.L. Rominguera, M. Murcia, J.A. Ramos, and A. Viso Tetrahedron 56 2000 3245
41. R.D. Clark, K.K. Weinhardt, J. Berger, L.E. Fischer, C.M. Brown, A.C. MacKinnon, A.T. Kilpatrick, and M. Spedding J. Med. Chem. 33 1990 633
42. D.T. Wong, D.W. Robertson, and L.R. Reid Eur. J. Pharmacol. 166 1989 107
43. E. Ambrosio, M.T. Montero, I. Fernández, M.C. Azuara, and L.M. Orensanz Neurosci. Lett. 49 1984 193
44. H. Hall, I. Wedel, and M. Sällemark Pharmacol. Toxicol. 63 1988 118
45. Y. Cheng, and W.H. Prusoff Biochem. Pharmacol. 22 1973 3099
46. O.H. Lowry, N.J. Rosebrough, A.L. Farr, and R.J. Randall J. Biol. Chem. 193 1951 265
47. R.H. Alper, and D.L. Nelson Eur. J. Pharmacol. 343 1998 303
48. W.D. Paton, and E.S. Vizi Br. J. Pharmacol. 35 1969 10
49. I. Artaiz, A. Zazpe, and J. Del Rí-o Behav. Pharmacol. 9 1998 103
50. I. Artaiz, G. Romero, A. Zazpe, A. Monge, J.M. Calderó, J. Roca, B. Lasheras, and J. Del Rí-o Psychopharmacology 117 1995 137