Novel 5-HT7 receptor inverse agonists. Synthesis and molecular modeling of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides

Journal of Medicinal Chemistry

Volumn 47, Issue 22, 2004, Pages 5451-5466

  Vermeulen, Erik S ^a   Van Smeden, Marjan ^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

ADENYLATE CYCLASE; G PROTEIN COUPLED RECEPTOR; N ETHYL 4 METHOXY N [3 (6 METHOXY 3,4 DIHYDRO 1H ISOQUINOLIN 2 YL)PROPYL]BENZENESULFONAMIDE; N ETHYL N [3 (6 METHOXY 3,4 DIHYDRO 1H ISOQUINOLIN 2 YL)PROPYL] 4 METHYLBENZENESULFONAMIDE; N ETHYL N [3 (6 METHOXY 3,4 DIHYDRO 1H ISOQUINOLIN 2 YL)PROPYL]BENZENESULFONAMIDE; N ETHYL N [3 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]PROPYL] 4 METHYLBENZENESULFONAMIDE; NAPHTHALENE 1 SULFONIC ACID ETHYL [3 (6 METHOXY 3,4 DIHYDRO 1H ISOQUINOLIN 2 YL)PROPYL]AMIDE; PIPERAZINE DERIVATIVE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; SEROTONIN 7 RECEPTOR; SEROTONIN AGONIST; SULFONAMIDE; TETRAHYDROISOQUINOLINE DERIVATIVE; UNCLASSIFIED DRUG; ISOQUINOLINE DERIVATIVE; LIGAND; SEROTONIN RECEPTOR;

ARTICLE; DRUG BINDING SITE; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SYNTHESIS; ENZYME ACTIVITY; GENE EXPRESSION; HUMAN; HUMAN CELL; MOLECULAR INTERACTION; MOLECULAR MODEL; PHARMACOPHORE; STRUCTURE ACTIVITY RELATION; ANIMAL; BINDING SITE; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RADIOASSAY; RAT; SYNTHESIS;

ADENYLATE CYCLASE; ANIMALS; BINDING SITES; CELL LINE; HUMANS; ISOQUINOLINES; LIGANDS; MODELS, MOLECULAR; PIPERAZINES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RADIOLIGAND ASSAY; RATS; RECEPTORS, SEROTONIN; SEROTONIN AGONISTS; SULFONAMIDES;

EID: 6044276744     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049743b     Document Type: Article

References (48)

1. Pallas. [Version 1.2]. 1994. CompuDrug Chemistry Ltd.
2. MacroModel. [Version 7.0]. 1999. Schrodinger Inc.
3. Sybyl Molecular Modeling Software. [Version 6.8]. 2001. Tripos, Inc.
4. Allinger, N. L.; Yuh, Y. H.; Lu, J.-H. Molecular mechanics. The MM3 force field for hydrocarbons. 1. J. Am. Chem. Soc. 1989, 111, 8551-8566.
5. 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.
6. 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.
7. 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.
8. Bojarski, A. J.; Mokrosz, M. J. 1,2,3,4-Tetrahydroisoquinoline derivatives; lipophilicity evaluation vs 5-HT1A receptor affinity. Pharmazie 1999, 54, 828-830.
9. Bojarski, A. J.; Mokrosz, M. J.; Minol, S. C.; Koziol, A.; Wesolowska, A.; Tatarczynska, E.; Klodzinska, A.; Chojnacka-Wojcik, E. The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT(1A)/5-HT-(2A) receptor activities of its 1-adamantoyloaminoalkyl derivatives. Bioorg. Med. Chem. 2002, 10, 87-95.
10. 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.
11. Decker, H.; Becker, P. Liebigs Ann. Chem. 1913, 395, 342.
12. 7 receptor antagonist. J. Med. Chem. 1998, 41, 655-657.
13. Forbes, I. T.; Douglas, S.; Gribble, A. D.; Ife, R. J.; Lightfoot, A. P.; Garner, A. E.; Riley, G. J.; Jeffrey, P.; Stevens, A. J.; Stean, T. O.; Thomas, D. R. SB-656104-A: a novel 5-HT(7) receptor antagonist with improved in vivo properties. Bioorg. Med. Chem. Lett. 2002, 12, 3341-3344.
14. Goodman, J.; Still, W. C. An unbounded systematic search of conformational space. J. Comput. Chem. 1991, 12, 1110-1117.
15. Hagan, J. J.; Price, G. W.; Jeffrey, P.; Deeks, N. J.; Stean, T.; Piper, D.; Smith, M. I.; Upton, N.; Medhurst, A. D.; Middlemiss, D. N.; Riley, G. J.; Lovell, P. J.; Bromidge, S. M.; Thomas, D. R. Characterization of SB-269970-A, a selective 5-HT7 receptor antagonist. Br. J. Pharmacol. 2000, 130, 539-548.
16. 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.
17. Kikuchi, C.; Ando, T.; Watanabe, T.; Nagaso, H.; Okuno, M.; Hiranuma, T.; Koyama, M. 2a-[4-(Tetrahydropyridoindol-2-yl)-butyl]tetrahydrobenzindole derivatives: new selective antagonists of the 5-hydroxytryptamine7 receptor. J. Med. Chem 2002, 45, 2197-2206.
18. Kikuchi, C.; Hiranuma, T.; Koyama, M. Tetrahydrothienopyridylbutyl- tetrahydrobenzindoles: new selective ligands of the 5-HT(7) receptor. Bioorg. Med. Chem. Lett. 2002, 12, 2549-2552.
19. Kikuchi, C.; Nagaso, H.; Hiranuma, T.; Koyama, M. Tetrahydrobenzindoles: Selective antagonists of the 5-HT7 receptor. J. Med. Chem. 1999, 42, 533-535.
20. Kikuchi, C.; Suzuki, H.; Hiranuma, T.; Koyama, M. New tetrahydrobenzindoles as potent and selective 5-HT7 antagonists with increased In vitro metabolic stability. Bioorg. Med. Chem. Lett. 2003, 13, 61-64.
21. Krobert, K. A.; Bach, T.; Syversveen, T.; Kvingedal, A. M.; Levy, F. O. The cloned human 5-HT7 receptor splice variants: A comparative characterization of their pharmacology, function and distribution. Naunyn S. Arch. Pharmacol. 2001, 363, 620-632.
22. Krobert, K. A.; Levy, F. O. The human 5-HT7 serotonin receptor splice variants: constitutive activity and inverse agonist effects. Br. J. Pharmacol. 2002, 135, 1563-1571.
23. 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.
24. 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.
25. Linnanen, T.; Brisander, M.; Unelius, L.; Rosqvist, S.; Nordvall, G.; Hacksell, U.; Johansson, A. M. Atropisomeric derivatives of 2′′, 6′-disubstituted (R)-11-phenylaporphine: selective serotonin 5-HT(7) receptor antagonists. J. Med. Chem. 2001, 44, 1337-1340.
26. 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.
27. Lopez-Rodriguez, M. L.; Porras, E.; Morcillo, M. J.; Benhamu, B.; Soto, L. J.; Lavandera, J. L.; Ramos, J. A.; Olivella, M.; Campillo, M.; Pardo, L. Optimization of the pharmacophore model for 5-HT7R antagonism. Design and synthesis of new naphtholactam and naphthosultam derivatives. J. Med. Chem. 2003, 46, 5638-5650.
28. Lovell, P. J.; Bromidge, S. M.; Dabbs, S.; Duckworth, D. M.; Forbes, I. T.; Jennings, A. J.; King, F. D.; Middlemiss, D. N.; Rahman, S. K.; Saunders: D. V.; Collin, L. L.; Hagan, J. J.; Riley, G. J.; Thomas, D. R. A novel, potent, and selective 5-HT7 antagonist: (R)-3-(2-(2-(4-methylpiperidin-l-yl)-ethyl) pyrrolidine-1-sulfonyl)phenol (SB-269970). J. Med. Chem. 2000, 43, 342-345.
29. 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.
30. Mokrosz, J. L.; Bojarski, A. J.; Charakchieva-Minol, S.; Duszynska, B.; Mokrosz, M. J.; Paluchowska, M. H. Structure-activity relationship studies of CNS agents, Part 23: N-(3-phenylpropyl)- and N-[(E)-cinnamyl]-l,2,3,4- tetrahydroisoquinoline mimic 1-phenylpiperazine at 5-HT1A receptors. Arch. Pharm. (Weinheim) 1995, 328, 604-608.
31. Mokrosz, J. L.; Deren-Wesolek, A.; Tatarczynska, E.; Duszynska, B.; Bojarski, A. J.; Mokrosz, M. J.; Chojnacka-Wojcik, E. 8-[4-[2-(1,2,3,4- Tetrahydroisoquinolinyl]butyl-8-azaspiro [4.5]-decane -7,9-dione: a new 5-HT1A receptor ligand with the same activity profile as buspirone. J. Med. Chem. 1996, 39, 1125-1129.
32. Mokrosz, M. J.; Bojarski, A. J.; Duszynska, B.; Tatarczynska, E.; Klodzinska, A.; Deren-Wesolek, A.; Charakchieva-Minol, S.; Chojnacka-Wojcik, E. 1,2,3,4-tetrahydroisoquinoline derivatives: a new class of 5-HT1A receptor ligands. Bioorg. Med. Chem 1999, 7, 287-295.
33. Paluchowska, M. H.; Bojarski, A. J.; Charakchieva-Minol, S.; Wesolowska, A. Active conformation of some arylpiperazine postsynaptic 5-HT(1A) receptor antagonists. Eur. J. Med. Chem. 2002, 37, 273-283.
34. Perrone, R.; Berardi, F.; Colabufo, N. A.; Lacivita, E.; Leopoldo, M.; Tortorella, V. Synthesis and structure-affinity relationships of 1-[omega-(4-aryl-1-piperazinyl)alkyl]-1-aryl ketones as 5-HT-(7) receptor ligands. J. Med. Chem. 2003, 46, 646-649.
35. Plassat, J. L.; Amlaiky, N.; Hen, R. Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase. Mol. Pharmacol. 1993, 44, 229-236.
36. 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.
37. Salomon, Y. Adenylate cyclase assay. Adv. Cyclic Nucleotide Res. 1979, 10, 35-55.
38. Shapiro, D. A.; Kristiansen, K.; Kroeze, W. K.; Roth, B. L. Differential modes of agonist binding to 5-hydroxytryptamine-(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5. Mol. Pharmacol. 2000, 58, 877-886.
39. 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.
40. 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.
41. Speeter, M. E.; Anthony, W. C. The action of oxalyl chloride on indoles: a new approach to tryptamines. J. Am. Chem Soc. 1954, 76, 6208-6210.
42. Steiner, T.; Koellner, G. Hydrogen Bonds with p-Acceptors in Proteins: Frequencies and Role in Stabilizing Local 3-D Structures. J. Biol. Chem. 2001, 305, 535-557.
43. Still, W. K.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. Semianalytical treatment of solvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 1990, 112, 6127-6129.
44. Thomas David, R.; Gittins Susan, A.; Collin Lissa, L.; Middlemiss Derek, N.; Riley Graham; Hagan Jim; Gloger Israel; Ellis Catherine, E.; Forbes Ian, T.; Brown Anthony, M. Functional characterisation of the human cloned 5-HT7 receptor (long form): Antagonist profile of SB-258719. Br. J. Pharmacol. 1998, 124, 1300-1306.
45. Thomas, D. R.; Atkinson, P. J.; Hastie, P. G.; Roberts, J. C.; Middlemiss, D. N.; Price, G. W. [3H]-SB-269970 radiolabels 5HT7 receptors in rodent, pig and primate brain tissues. Neuropharmacology 2002, 42, 74-81.
46. Thomas, D. R.; Atkinson, P. J.; Ho, M.; Bromidge, S. M.; Lovell, P. J.; Villani, A. J.; Hagan, J. J.; Middlemiss, D. N.; Price, G. W. [H-3]-SB-269970 - A selective antagonist radioligand for 5-HT7 receptors. Br. J. Pharmacol. 2000, 730, 409-417.
47. Vermeulen, E. S.; Schmidt, A. W.; Sprouse, J. S.; Wikstrom, H. V.; Grol, C. J. Characterization of the 5-HT(7) receptor. Determination of the pharmacophore for 5-HT(7) receptor agonism and CoMFA-based modeling of the agonist binding site. J. Med. Chem. 2003, 46, 5365-5374.
48. Wesolowska, A. In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. Pol. J. Pharmacol. 2002, 54, 327-341.