A three-dimensional pharmacophore model for 5-hydroxytryptamine6 (5-HT6) receptor antagonists

Journal of Medicinal Chemistry

Volumn 48, Issue 13, 2005, Pages 4216-4219

  López Rodríguez, María L ^a   Benhamú, Bellinda ^a   De La Fuente, Tania ^a   Sanz, Arantxa ^b   Pardo, Leonardo ^b   Campillo, Mercedes ^b  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b INSTITUT DE NEUROCIÈNCIES   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC COMPOUND; ASPARAGINE; ASPARTIC ACID; MEMBRANE PROTEIN; PHENYLALANINE; SERINE; SEROTONIN 6 RECEPTOR; SEROTONIN ANTAGONIST;

ARTICLE; CATALYST; COMPUTER PROGRAM; DRUG ANTAGONISM; DRUG SELECTIVITY; DRUG STRUCTURE; HYDROGEN BOND; HYDROPHOBICITY; PHARMACOPHORE;

EID: 21244446301     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050247c     Document Type: Article

References (45)

1. Roth, B. L.; Lopez, E.; Patel, S.; Kroeze, W. K. The Multiplicity of Serotonin Receptors: Uselessly Diverse Molecules or an Embarrassment of Riches? Neuroscientist 2000, 6, 252-262.
2. Hoyer, D.; Hannon, J. P. Molecular, Pharmacological and Functional Diversity of 5-HT Receptors. Pharmacol. Biochem. Behav. 2002, 71, 533-554.
3. Jones, B. J.; Blackburn, T. P. The Medical Benefit of 5-HT Research. Pharmacol. Biochem. Behav. 2002, 71, 555-568.
4. Uphouse, L. Multiple Serotonin Receptors: Too Many, Not Enough, or Just the Right Number? Neurosci. Biobehav. Rev. 1997, 21, 679-698.
5. Bikker, J. A.; Trump-Kallmeyer, S.; Humblet, S. G-Protein Coupled Receptors: Models, Mutagenesis, and Drug Design. J. Med. Chem. 1998, 41, 2911-2927.
6. 7. J. Med. Chem. 2003, 46, 2795-2812.
7. Monsma, F. J.; Shen, Y.; Ward, R. P.; Hamblin, M. W.; Sibley, D. R. Cloning and Expression of a Novel Serotonin Receptor with High Affinity for Tricyclic Psychotropic Drugs. Mol. Pharmacol. 1993, 43, 320-327.
8. 6) Receptor. Molecular-Cloning, Localization and Stimulation of cAMP Accumulation. Biochem. Biophys. Res. Commun. 1993, 193, 268-276.
9. 6 Receptors Positively Coupled to Adenylyl Cyclase in Striatal Neurones in Culture. NeuroReport 1994, 5, 2553-2557.
10. 3 Serotonin Receptor. J. Neurochem. 1996, 66, 47-56.
11. 6 Receptor: Localization and Function. Ann. N.Y. Acad. Sci. 1998, 861, 91-96.
12. Hirst, W. D.; Abrahamsen, B.; Blaney, F. E.; Calver, A. R.; Aloj, L.; Price, G. W.; Medhurst, A. D. Differences in the Central Nervous System Distribution and Pharmacology of the Mouse 5-Hydroxytryptamine-6 Receptor Compared with Rat and Human Receptors Investigated by Radioligand Binding, Site-Directed Mutagenesis, and Molecular Modeling. Mol. Pharmacol. 2003, 64, 1295-1308.
13. 6 Receptor Antagonists for the Treatment of CNS Diseases. Expert Opin. Ther. Pat. 2002, 12, 513-527.
14. 6 Antagonists for Cognitive Disorders. Drug Discovery Today 2001, 6, 489.
15. 6 Receptors as Emerging Targets for Drug Discovery. Annu. Rev. Pharmacol. Toxicol. 2000, 40, 319-334.
16. 6 Receptor Ligands and Their Biological Functions. Curr. Top. Med. Chem. 2002, 2, 643-654.
17. 7 Serotonin Receptors. Pol. J. Pharmacol. 2002, 54, 327-341.
18. Kurogi, Y.; Güner, O. F. Pharmacophore Modeling and Three-Dimensional Database Searching for Drug Design Using Catalyst. Curr. Med. Chem. 2001, 8, 1035-1055.
19. Güner, O.; Clement, O.; Kurogi, Y. Pharmacophore Modeling and Three-Dimensional Database Searching for Drug Design Using Catalyst: Recent Advances. Curr. Med. Chem. 2004, 11, 2991-3005.
20. Catalyst, version 4.9; Molecular Simulations Inc.: San Diego, CA, 2003.
21. 7R Antagonism. Design and Synthesis of New Naphtholactam and Naphthosultam Derivatives. J. Med. Chem. 2003, 46, 5638-5650.
22. 6 Receptor Antagonists: Lead Optimisation and Biological Evaluation of N-Aryl and N-Heteroaryl 4-Aminobenzene Sulfonamides. Eur. J. Med. Chem. 2001, 36, 165-178.
23. 6 Receptor Antagonist. J. Med. Chem. 1999, 42, 202-205.
24. 6 Receptor Antagonists. Bioorg. Med. Chem. Lett. 2002, 12, 1357-1360.
25. 6 Receptor. Bioorg. Med. Chem. Lett. 2001, 11, 2843-2846.
26. 6 Antagonists: Identification of N-(2,5-Dibromo-3-fluorophenyl)-4-methoxy-3- piperazin-1-ylbenzene-sulfonamide (SB-357134). Bioorg. Med. Chem. Lett. 2001, 11, 55-58.
27. 6 Receptor Ligands. J. Med. Chem. 2005, 48, 1781-1795.
28. 6 Receptor. U.S. Patent 2004/0102481, 2004.
29. 6 Antagonist: One-Step Synthesis of (E)-3-(Benzenesulfonyl)-2-(methylsulfanyl)pyrido[1,2-a]pyrimidin-4- ylidenamine from 2-(Benzenesulfonyl)-3,3-bis(methylsulfanyl)acrylonitrile. J. Med. Chem. 2003, 46, 4834-4837.
30. 6 Receptor Antagonist. J. Med. Chem. 2003, 46, 1273-1276.
31. 6 Receptor Affinity. PCT Int. Appl. WO 03/014097, 2003.
32. 6 Modulators. PCT Int. Appl. WO 2004/026831, 2004.
33. 6 Antagonists. Bioorg. Med. Chem. Lett. 2000, 10, 2295-2299.
34. 6 Receptor Antagonists. Bioorg. Med. Chem. Lett. 2000, 10, 1719-1721.
35. 6 Receptor Ligands. J. Med. Chem. 2001, 44, 3881-3895.
36. 6 Receptor Ligand Templates. Bioorg. Med. Chem. Lett. 2003, 13, 3355-3359.
37. 6 Serotonin Receptor Ligands. Bioorg. Med. Chem. Lett. 2004, 14, 1961-1964.
38. 6 Serotonin Receptors. J. Med. Chem. 2000, 43, 1011-1018.
39. Shi, L.; Javitch, J. A. The Binding Site of Aminergic G Protein-Coupled Receptors: The Transmembrane Segments and Second Extracellular Loop. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 437-467.
40. Ballesteros, J. A.; Weinstein, H. Integrated Methods for the Construction of Three Dimensional Models and Computational Probing of Structure-Function Relations in G-Protein Coupled Receptors. Methods Neurosci. 1995, 25, 366-428.
41. Li, J.; Edwards, P. C.; Burghammer, M.; Villa, C.; Schertler, G. F. Structure of Bovine Rhodopsin in a Trigonal Crystal Form. J. Mol. Biol. 2004, 343, 1409-1438.
42. Lopez-Rodriguez, M. L.; Vicente, B.; Deupi, X.; Barrondo, S.; Olivella, M.; Morcillo, M. J.; Benhamu, B.; Ballesteros, J. A.; Salles, J.; Pardo, L. Design, Synthesis and Pharmacological Evaluation of 5-Hydroxytryptamine(1a) Receptor Ligands to Explore the Three-Dimensional Structure of the Receptor. Mol. Pharmacol. 2002, 62, 15-21.
43. Shi, L.; Javitch, J. A. The Second Extracellular Loop of the Dopamine D2 Receptor Lines the Binding-Site Crevice. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 440-445.
44. Canutescu, A. A.; Shelenkov, A. A.; Dunbrack, R. L., Jr. A Graph-Theory Algorithm for Rapid Protein Side-Chain Prediction. Protein Sci. 2003, 12, 2001-2014.
45. Case, D. A.; Darden, T. A.; Cheatham, T. E., III; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Merz, K. M.; Wang, B.; Pearlman, D. A.; Crowley, M.; Brozell, S.; Tsui, V.; Gohlke, H.; Mongan, J.; Hornka, V.; Cui, G.; Beroza, P.; Schafmeister, C.; Caldwell, J. W.; Ross, W. S.; Kollman, P. A. AMBER, version 8; University of California: San Francisco, 2003.