Characterization of the 5-HT7 Receptor. Determination of the Pharmacophore for 5-HT7 Receptor Agonism and CoMFA-Based Modeling of the Agonist Binding Site

Journal of Medicinal Chemistry

Volumn 46, Issue 25, 2003, Pages 5365-5374

  Vermeulen, Erik S ^a   Schmidt, Anne W ^b   Sprouse, Jeffrey S ^b   Wikström, Håkan V ^a   Grol, Cor J ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SEROTONIN 7 RECEPTOR; SEROTONIN 7 RECEPTOR AGONIST; SEROTONIN AGONIST; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CORRELATION ANALYSIS; DRUG BINDING; DRUG BINDING SITE; DRUG DISTRIBUTION; DRUG STRUCTURE; HYDROGEN BOND; LIPOPHILICITY; MODEL; PHARMACOPHORE; PROTON TRANSPORT; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

BINDING SITES; LIGANDS; MODELS, MOLECULAR; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RECEPTORS, SEROTONIN; SEROTONIN AGONISTS; TETRAHYDRONAPHTHALENES; TRYPTAMINES;

EID: 0344550379     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030826m     Document Type: Article

References (42)

1. Vanhoenacker, P.; Haegeman, G.; Leysen, J. E. 5-HT7 receptors: Current knowledge and future prospects. Trends. Pharmacol. Sci. 2000, 21, 70-77.
2. Eglen, R. M.; Jasper, J. R.; Chang, D. J.; Martin, G. R. The 5-HT7 receptor: Orphan found. Trends. Pharmacol. Sci 1997, 18, 104-107.
3. Terron, J. A. The 5-HT7 receptor: A target for novel therapeutic avenues? Drugs 1998, 1, 302-310.
4. Bard, J. A.; Zgombick, J.; Adham, N.; Vaysse, P.; Branchek, T. A.; Weinshank, R. L. Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J. Biol Chem. 1993, 268, 23422-23426.
5. Ruat, M.; Traiffort, E.; Leurs, R.; Tardivel Lacombe, J.; Diaz, J.; Arrang, J.; Schwartz, J. C. Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. Proc. Natl. Acad. Sci U.S.A. 1993, 90, 8547-8551.
6. Heidmann, D. E.; Metcalf, M. A.; Kohen, R.; Hamblin, M. W. Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: Species differences due to altered intron-exon organization. J. Neurochem. 1997, 68, 1372-1381.
7. Jasper, J. R.; Kosaka, A.; To, Z. P.; Chang, D. J.; Eglen, R. M. Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b). Br. J. Pharmacol. 1997, 122, 126-132.
8. Stam, N. J.; Roesink, C.; Dijcks, F.; Garritsen, A.; van Herpen, A.; Olijve, W. Human serotonin 5-HT7 receptor: Cloning and pharmacological characterisation of two receptor variants. FEBS Lett. 1997, 413, 489-494.
9. Forbes, I. T.; Dabbs, S.; Duckworth, D. M.; Jennings, A. J.; King, F. D. ; Lovell, P. J.; Brown, A. M.; Collin, L.; Hagan, J. J.; Middlemiss, D. N.; Riley, G. J.; Thomas, D. R.; Upton, N. (R)-3,N-dimethyl-N-[1-methyl-3-(4-methyl-piperidin-1-yl)propyl] ben-zenesulfonamide: The first selective 5-HT7 receptor antagonist. J. Med. Chem. 1998, 41, 655-657.
10. Linnanen, T. Serotonergic Aporphine Derivatives, Thesis, Uppsala University, 2000.
11. Kikuchi, C.; Nagaso, H.; Hiranuma, T.; Koyama, M. Tetrahydrobenzindoles: Selective antagonists of the 5-HT7 receptor. J. Med. Chem. 1999, 42, 533-535.
12. Lopez-Rodriguez, M. L.; Porras, E.; Benhamu, B.; Ramos, J. A.; Morcillo, M. J.; Lavandera, J. L. First pharmacophoric hypothesis for 5-HT7 antagonism. Bioorg. Med. Chem. Lett. 2000, 10, 1097-1100.
13. Lovenberg, T. W.; Baron, B. M.; de Lecea, L.; Miller, J. D.; Prosser, R. A.; Rea, M. A.; Foye, P. E.; Racke, M.; Slone, A. L.; Siegel, B. W. A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 1993, 11, 449-458.
14. Jacobs, E. H.; Yamatodani, A.; Timmerman, H. Is histamine the final neurotransmitter in the entrainment of circadian rhythms in mammals? Trends. Pharmacol. Sci. 2000, 21, 293-298.
15. Ying, S. W.; Rusak, B. 5-HT7 receptors mediate serotonergic effects on light-sensitive suprachiasmatic nucleus neurons. Brain Res. 1997, 755, 246-254.
16. Mullins, U. L.; Gianutsos, G.; Eison, A. S. Effects of antidepressants on 5-HT7 receptor regulation in the rat hypothalamus. Neuropsychopharmacology 1999, 21, 352-367.
17. Duncan, M. J.; Short, J.; Wheeler, D. L. Comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters. Brain Res. 1999, 829, 39-45.
18. Yau, J. L.; Noble, J.; Widdowson, J.; Seckl, J. R. Impact of adrenalectomy on 5-HT6 and 5-HT7 receptor gene expression in the rat hippocampus. Mol. Brain Res. 1997, 45, 182-186.
19. Shimizu, M.; Nishida, A.; Zensho, H.; Yamawaki, S. Chronic antidepressant exposure enhances 5-hydroxytryptamine7 receptor-mediated cyclic adenosine monophosphate accumulation in rat frontocortical astrocytes. J. Pharmacol. Exp. Ther. 1996, 279, 1551-1558.
20. Terron, J. A.; Falcon Neri, A. Pharmacological evidence for the 5-HT7 receptor mediating smooth muscle relaxation in canine cerebral arteries. Br. J. Pharmacol. 1999, 127, 609-616.
21. De Vries, P.; De Visser, P. A.; Heiligers, J. P. C.; Villalon, C. M.; Saxena, P. R. Changes in systemic and regional haemodynamics during 5-HT7 receptor-mediated depressor responses in rats. Naunyn S. Arch. Pharmacol. 1999, 359, 331-338.
22. Wilcox, R. E.; Ragan, J. E.; Pearlman, R. S.; Brusniak, M. Y.; Eglen, R. M.; Bonhaus, D. W.; Miller, J. D. High-affinity interactions of ligands at recombinant guinea pig 5HT7 receptors. J. Comput. Aided Mol. Des. 2001, 15, 883-909.
23. Baldwin, J. M.; Schertler, G. F. X.; Unger, V. M. An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. J. Mol. Biol. 1997, 272, 144-164.
24. Parikh, V.; Welch, W. M.; Schmidt, A. W. Discovery of a series of (4,5-Dihydroimidazol-2-yl)-biphenylamine 5-HT(7) agonists. Bioorg. Med. Chem. Lett. 2003, 13, 269-271.
25. Plassat, J. L.; Amlaiky, N.; Hen, R. Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol. Pharmacol. 1993, 44, 229-236.
26. Sanin, A.; Brisander, M.; Rosqvist, S.; Mohell, N.; Malmberg, A.; Johansson, A. M., 5-Aryl substituted (S)-2-(dimethylamino)-tetralines. Novel serotonin 5-HT7 receptor ligands, poster at XVIIth Int. Symp. Medicinal Chemistry, Barcelona, 2002.
27. Shen, Y.; Monsma, F. J., Jr.; Metcalf, M. A.; Jose, P. A.; Hamblin, M. W.; Sibley, D. R. Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J. Biol Chem. 1993, 268, 18200-18204.
28. MacroModel, Version 7.0.; Schrodinger Inc., 1999.
29. Snyder, J. P.; Rao, S. N.; Koehler, K. F.; Vedani, A.; Pelliciari, R. APOLLO Pharmacophores and the pseudoreceptor concept, in Trends in QSAR and Molecular Modeling 92, Wermuth, C. G., Ed.; ESCOM: Leiden, 1993; pp 44-51.
30. Sybyl Molecular Modeling Software, Version 6.8; Tripos, Inc., 2001.
31. Javitch, J. A.; Ballesteros, J. A.; Weinstein, H.; Chen, J. A cluster of aromatic residues in the sixth membrane-spanning segment of the dopamine D2 receptor is accessible in the binding-site crevice. Biochemistry 1998, 37, 998-1006.
32. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; Fox, B. A.; Le, T. I.; Teller, D. C.; Okada, T.; Stenkamp, R. E.; Yamamoto, M.; Miyano, M. Crystal structure of rhodopsin: A G protein-coupled receptor [see comments]. Science 2000, 289, 739-745.
33. Lopez-Rodriguez, M. L.; Vicente, B.; Deupi, X.; Barrondo, S.; Olivella, M.; Morcillo, M. J.; Behamu, B.; Ballesteros, J. A.; Salles, J.; Pardo, L. Design, synthesis and pharmacological evaluation of 5-hydroxytryptamine(la) receptor ligands to explore the three-dimensional structure of the receptor. Mol. Pharmacol. 2002, 62, 15-21.
34. Rim, J.; Oprian, D. D. Constitutive activation ofopsin: Interaction of mutants with rhodopsin kinase and arrestin. Biochemistry 1995, 34, 11938-11945.
35. Homan, E. J.; Wikstrom, H. V.; Grol, C. J. Molecular modeling of the dopamine D2 and serotonin 5-HT1A receptor binding modes of the enantiomers of 5-OMe-BPAT. Bioorg. Med. Chem. 1999, 7, 1805-1820.
36. Chang, G.; Guida, W. C.; Still, W. C. An internal-coordinate Monte Carlo method for searching conformational space. J. Am. Chem. Soc. 1989, 111, 4379-4386.
37. Goodman, J.; Still, W. C. An unbounded systematic search of conformational space. J. Comput. Chem. 1991, 12, 1110-1117.
38. Allinger, N. L.; Yuh, Y. H.; Lii, J.-H. Molecular mechanics. The MM3 force field for hydrocarbons. 1. J. Am. Chem. Soc. 1989, 111, 8551-8566.
39. Lii, J.-H.; Allinger, N. L. Molecular mechanics. The MM3 force field for hydrocarbons. 2. Vibrational frequencies and thermodynamics. J. Am. Chem. Soc. 1989, 111, 8566-8575.
40. Lii, J.-H.; Allinger, N. L. Molecular mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals' potentials and crystal data for aliphatic and aromatic hydrocarbons. J. Am. Chem. Soc. 1989, 111, 8576-8582.
41. Still, W. K.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. Semianalytical treatment of salvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 1990, 112, 6127-6129.
42. Salomon, Y. Adenylate Cyclase Assay. Adv. Cyclic Nucleotide Res. 1979, 10, 35-55.