5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists

Journal of Medicinal Chemistry

Volumn 53, Issue 6, 2010, Pages 2521-2527

  Haydar, Simon N ^a   Yun, Heedong ^a   Andrae, Patrick M ^a   Mattes, James ^a   Zhang, Jean ^a   Kramer, Angela ^a   Smith, Deborah L ^a   Huselton, Christine ^a   Graf, Radka ^a   Aschmies, Suzan ^a   Schechter, Lee E ^a   Comery, Thomas A ^a   Robichaud, Albert J ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 (1 NAPHTHYLSULFONYL) 1H INDAZOL 5 YL]AZETIDIN 3 AMINE; 1 [3 (1 NAPHTHYLSULFONYL) 1H INDAZOL 5 YL]PIPERIDIN 4 AMINE; 1 [3 (2 NAPHTHYLSULFONYL) 1H INDAZOL 5 YL]PIPERIDIN 4 AMINE; 1 [3 [(4 ISOPROPYLPHENYL)SULFONYL] 1H INDAZOL 5 YL]PIPERIDIN 4 AMINE; 1 [3 [(4 METHYL 1 NAPHTHYL)SULFONYL] 1H INDAZOL 5 YL]PIPERIDIN 4 AMINE; 1 [3 [(5 CHLORO 1 NAPHTHYL)SULFONYL] 1H INDAZOL 5 YL]PIPERIDIN 4 AMINE; 1 PIPERIDIN 4 AMINE; 3 1 [1 (1 METHYLETHYL) 3 (NAPHTHALEN 1 YLSULFONYL) 1H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 1 [1 (2 METHYLPROPYL) 3 (NAPHTHALEN 1 YLSULFONYL) 1H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 1 [1 METHYL 3 (NAPHTHALEN 1 YLSULFONYL) 1H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 1 [2 (1 METHYLETHYL) 3 (NAPHTHALEN 1 YLSULFONYL) 2H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 1 [2 (2 METHYLPROPYL) 3 (NAPHTHALEN 1 YLSULFONYL) 2H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 1 [2 METHYL 3 (NAPHTHALEN 1 YLSULFONYL) 2H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 1 [3 (1 NAPHTHYLSULFONYL) 1H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 3 N,N DIMETHYL 1 [3 (1 NAPHTHYLSULFONYL) 1H INDAZOL 5 YL]PYRROLIDIN 3 AMINE; 5 CYCLIC AMINE 3 ARYLSULFONYLINDAZOLE DERIVATIVE; G PROTEIN COUPLED RECEPTOR; SEROTONIN 6 ANTAGONIST; UNCLASSIFIED DRUG;

ALKYLATION; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; COGNITION; CONTROLLED STUDY; DRUG IDENTIFICATION; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HELA CELL; HUMAN; HUMAN CELL; NONHUMAN; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING, COMPETITIVE; BRAIN; EXPLORATORY BEHAVIOR; HABITUATION, PSYCHOPHYSIOLOGIC; HUMANS; INDAZOLES; MODELS, CHEMICAL; MOLECULAR STRUCTURE; RATS; RECEPTOR, SEROTONIN, 5-HT2B; RECEPTORS, SEROTONIN; RECOGNITION (PSYCHOLOGY); SEROTONIN ANTAGONISTS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

EID: 77949806521     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901674f     Document Type: Article

References (24)

1. Gerard, C.; Martres, M. P.; Lefevre, K.; Miquel, M. C.; Verge, D.; Lanfumey, L.; Doucet, E.; Hamon, M.; el Mestikawy, S. Immunolocalization of serotonin 5-HT6 receptor-like material in the rat central nervous system. Brain Res. 1997, 746 (1-2), 207-219.
2. Dawson, L. A.; Nguyen, H. Q.; Li, P. The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus. Neuropsychopharmacology 2001, 25 (5), 662-668.
3. Hirst, W. D.; Stean, T. O.; Rogers, D. C.; Sunter, D.; Pugh, P.; Moss, S. F.; Bromidge, S. M.; Riley, G.; Smith, D. R.; Bartlett, S.; Heidbreder, C. A.; Atkins, A. R.; Lacroix, L. P.; Dawson, L. A.; Foley, A. G.; Regan, C. M.; Upton, N. SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models. Eur. J. Pharmacol. 2006, 553 (1-3), 109-119.
4. Sleight, A. J.; Boess, F. G.; Bos, M.; Levet-Trafit, B.; Riemer, C.; Bourson, A. Characterization of Ro 04-6790 and Ro 63-0563: potent and selective antagonists at human and rat 5-HT6 receptors. Br. J. Pharmacol. 1998, 124 (3), 556-562.
5. Bromidge, S. M.; Brown, A. M.; Clarke, S. E.; Dodgson, K.; Gager, T.; Grassam, H. L.; Jeffrey, P. M.; Joiner, G. F.; King, F. D.; Middlemiss, D. N.; Moss, S. F.; Newman, H.; Riley, G.; Routledge, C.; Wyman, P. 5-Chloro-N-(4-methoxy-3-piperazin-1-ylphenyl)-3-methyl-2- benzothiophenesulfonamide (SB-271046): A potent, selective, and orally bioavailable 5-HT6 receptor antagonist. J. Med. Chem. 1999, 42 (2), 202-205.
6. Bromidge, S. M.; Clarke, S. E.; Gager, T.; Griffith, K.; Jeffrey, P.; Jennings, A. J.; Joiner, G. F.; King, F. D.; Lovell, P. J.; Moss, S. F.; Newman, H.; Riley, G.; Rogers, D.; Routledge, C.; Serafinowska, H.; Smith, D. R. Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134). Bioorg. Med. Chem. Lett. 2001, 11 (1), 55-58.
7. Russell, M.G.N.; Baker, R.J.; Barden, L.; Beer, M.S.; Bristow, L.; Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. N-Arylsulfonylindole derivatives as serotonin 5-HT6 receptor ligands. J. Med. Chem. 2001, 44 (23), 3881-3895.
8. Cole, D. C.; Lennox, W. J.; Stock, J. R.; Ellingboe, J. W.; Mazandarani, H.; Smith, D. L.; Zhang, G.; Tawa, G. J.; Schechter, L. E. Conformationally constrained N(l)-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists. Bioorg. Med. Chem. Lett. 2005, 15 (21), 4780-4785.
9. Cole, D. C.; Ellingboe, J. W.; Lennox, W. J.; Mazandarani, H.; Smith, D. L.; Stock, J. R.; Zhang, G.; Zhou, P.; Schechter, L. E. N1-Arylsulfonyl-3-(1,2, 3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists. Bioorg. Med. Chem. Lett. 2005, 15 (2), 379-383.
10. (a) Cole, D. C.; Lennox, W. J.; Lombardi, S.; Ellingboe, J. W.; Bernotas, R. C.; Tawa, G. J.; Mazandarani, H.; Smith, D. L.; Zhang, G.; Coupet, J.; Schechter, L. E. Discovery of 5-Arylsulfonamido-3-(pyrrolidin-2-ylmethyl)- 1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists. J. Med. Chem. 2005, 48 (2), 353-356.
11. (b) Liu, K. G.; Robichaud, A. J. 5-HT6 antagonists as potential treatment for cognitive dysfunction. Drug Dev. Res. 2009, 70 (2), 145-168.
12. Riemer, C.; Borroni, E.; Levet-Trafit, B.; Martin, J. R.; Poli, S.; Porter, R. H. P.; Boes, M. Influence of the 5-HT6 Receptor on Acetylcholine Release in the Cortex: Pharmacological Characterization of 4-(2-Bromo-6- pyrrolidin-1-ylpyridine-4-sulfonyl)phenylamine, a Potent and Selective 5-HT6 Receptor Antagonist. J. Med. Chem. 2003, 46 (7), 1273-1276.
13. Slassi, A.; Isaac, M.; O'Brien, A. Recent progress in 5-HT6 receptor antagonists for the treatment of CNS diseases. Expert Opin. Ther. Pat. 2002, 12 (4), 513-527.
14. East, S. Z.; Burnet, P. W. J.; Leslie, R. A.; Roberts, J. C.; Harrison, P. J. 5-HT6 receptor binding sites in schizophrenia and following antipsychotic drug administration: autoradiographic studies with [125I]SB-258585. Synapse (N. Y., NY, U. S.) 2002, 45 (3), 191-199.
15. Marcos, B.; Gil-Bea Francisco, J.; Hirst Warren, D.; GarciaAlloza, M.; Ramirez Maria, J. Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine release. Eur. J. Neurosci. 2006, 24 (5), 1299-1306.
16. Dawson, L. A.; Nguyen, H. Q.; Li, P. The 5-HT6 receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus. Neuropsychopharmacology 2001, 25 (5), 662-668.
17. Upton, N.; Chuang, T. T.; Hunter, A. J.; Virley, D. J. 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer's disease. Neurotherapeutics 2008, 5 (3), 458-469.
18. Holenz, J.; Merce, R.; Diaz, J. L.; Guitart, X.; Codony, X.; Dordal, A.; Romero, G.; Torrens, A.; Mas, J.; Andaluz, B.; Hernandez, S.; Monroy, X.; Sanchez, E.; Hernandez, E.; Perez, R.; Cubi, R.; Sanfeliu, O.; Buschmann, H. Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands. J. Med. Chem. 2005, 48 (6), 1781-1795.
19. Haydar, S. N.; Andrae, P. Aminoazacyclyl-3-sulfonylindazoles as 5-hydroxytryptamine-6 ligands. U.S. Pat. Appl. Publ. (2008), US 2008293688 A1 20081127, 2008
20. Antane, S.; Bernotas, R.; Li, Y.; McDevitt, R.; Yan, Y. Chloromethyl sulfones from sulfonyl chlorides via a one-pot procedure. Synth. Commun. 2004, 34 (13), 2443-2449.
21. Makosza, M.; Lemek, T.; Kwast, A.; Terrier, F. Elucidation of the vicarious nucleophilic substitution of hydrogen mechanism via studies of competition between substitution of hydrogen, deuterium, and fluorine. J. Org. Chem. 2002, 67 (2), 394-400.
22. Fitzgerald, L. W.; Burn, T. C.; Brown, B. S.; Patterson, J. P.; Corjay, M. H.; Valentine, P. A.; Sun, J.-H.; Link, J. R.; Abbaszade, I.; Hollis, J. M.; Largent, B. L.; Hartig, P. R.; Hollis, G. F.; Meunier, P. C.; Robichaud, A. J.; Robertson, D. W. Possible role of valvular serotonin 5-HT2B receptors in the cardiopathy associated with fenfluramine. Mol. Pharmacol. 2000, 57 (X), 75-81.
23. Di, L.; Kerns, E. H. Application of physicochemical data to support lead optimization by discovery teams. Biotechnol: Pharm. Aspects 2006, 4, 167-193.
24. Abraham, M. H.; Ibrahim, A.; Zissimos, A. M.; Zhao, Y. H.; Comer, J.; Reynolds, D. P. Application of hydrogen bonding calculations in property based drug design. Drug Discovery Today 2002, 7(20), 1056-1063.