Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors

ChemMedChem

Volumn 10, Issue 6, 2015, Pages 1054-1070

  Pau, Amedeo ^a   Catto, Marco ^b   Pinna, Giovanni ^a   Frau, Simona ^a   Murineddu, Gabriele ^a   Asproni, Battistina ^a   Curzu, Maria M ^a   Pisani, Leonardo ^b   Leonetti, Francesco ^b   Loza, Maria Isabel ^c   Brea, José ^c   Pinna, Gérard A ^a   Carotti, Angelo ^b  

^a UNIVERSITY OF SASSARI   (Italy)

^b UNIVERSITY OF BARI   (Italy)

^c Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela   (Spain)

Author keywords

AChE inhibitors; BChE inhibitors; GPCR ligands; multitarget directed ligands; neurodegenerative diseases

Indexed keywords

2 (4 BROMOBUTYL) 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 (5 BROMOPENTYL) 2,4,4A,5,6,7 HEXHYDRO 3H THIENO[2',3':6,7] CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 (6 BROMOHEXYL) 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 (7 BROMOHEPTYL) 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 [3 CHLOROPROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7] CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 [3 [4 (2 FLUOROPHENYL)PIPERAZIN 1 YL]PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 [3 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 2 [4 [4 METHYL PIPERAZIN 1 YL)BUTHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 (4 METHYLPIPERAZIN 1 YL)ETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 (4 METHYLPIPERIDIN 1 YL)ETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 (4 MORPHOLINE 1 YL)ETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 (4 PHENYLPIPERAZIN 1 YL)ETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 CHLOROETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO [2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 [4 (2 FLUOROPHENYL)PIPERAZIN 1 YL]ETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [2 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]ETHYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZINC3 ONE; 9 METHYL 2 [3 (4 METHYLPIPERAZIN 1 YL)PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [3 (4 METHYLPIPERIDIN 1 YL)PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [3 (4 MORPHOLINE 1 YL)PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3; 9 METHYL 2 [3 (4 PHENYLPIPERAZIN 1 YL)PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZ; 9 METHYL 2 [3 CHLOROPROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO [2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [3 [4 (2 FLUOROPHENYL)PIPERAZIN 1 YL)PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; 9 METHYL 2 [3 [4 (2 METHOXYPHENYL)PIPERAZIN 1 YL]PROPYL] 2,4,4A,5,6,7 HEXAHYDRO 3H THIENO[2',3':6,7]CYCLOHEPTA[1,2 C]PYRIDAZIN 3 ONE; CHOLINESTERASE INHIBITOR; DONEPEZIL; GALANTAMINE; HALOPERIDOL; LIGAND; PYRIDAZINONE DERIVATIVE; RISPERIDONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ACETYLCHOLINESTERASE; CHOLINESTERASE; G PROTEIN COUPLED RECEPTOR; PYRIDAZINE DERIVATIVE;

ALZHEIMER DISEASE; APPARENT PERMEABILITY; ARTICLE; BINDING ASSAY; CHOLINESTERASE INHIBITION; CONTROLLED STUDY; CYCLIZATION; DRUG BINDING SITE; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ELECTROPHORUS; HUMAN; HUMAN CELL; IC50; INHIBITION KINETICS; MOLECULAR RECOGNITION; MOLECULAR SIZE; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; ULTRAVIOLET SPECTROSCOPY; ANIMAL; DOG; DRUG EFFECTS; MDCK CELL LINE; METABOLISM;

ACETYLCHOLINESTERASE; ANIMALS; BUTYRYLCHOLINESTERASE; CHOLINESTERASE INHIBITORS; DOGS; HUMANS; LIGANDS; MADIN DARBY CANINE KIDNEY CELLS; PYRIDAZINES; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84930628127     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.201500124     Document Type: Article

References (47)

1. B. Bosier, E. Hermans, Trends Pharmacol. Sci. 2007, 28, 438-446.
2. B. Civantos Calzada, A. A. de Artiñano, Pharmacol. Res. 2001, 44, 195-208.
3. G. A. Michelotti, D. T. Price, D. A. Schwinn, Pharmacol. Ther. 2000, 88, 281-309.
4. L. E. Schechter, L. A. Dawson, J. A. Harder, Curr. Pharm. Des. 2002, 8, 139-145.
5. A. Meneses, Rev. Neurosci. 2014, 25, 325-356.
6. S. I. Sharp, C. G. Ballard, I. Ziabreva, M. A. Piggott, R. H. Perry, E. K. Perry, D. Aarsland, U. Ehrt, J. P. Larsen, P. T. Francis, Dementia Geriatr. Cognit. Disord. 2008, 26, 330-338.
7. Y. Ohno, Cent. Nerv. Syst. Agents Med. Chem. 2010, 10, 148-157.
8. R. Sandyk, Int. J. Neurosci. 2006, 116, 775-826.
9. J. Borg, Behav. Brain Res. 2008, 195, 103-111.
10. S. O. Ögren, T. M. Eriksson, E. Elvander-Tottie, C. D'Addario, J. C. Ekström, P. Svenningsson, B. Meister, J. Kehr, O. Stiedl, Behav. Brain Res. 2008, 195, 54-77.
11. L. E. Schechter, D. L. Smith, S. Rosenzweig-Lipson, S. J. Sukoff, L. A. Dawson, K. Marquis, D. Jones, M. Piesla, T. Andree, S. Nawoschik, J. A. Harder, M. D. Womack, J. Buccafusco, A. V. Terry, B. Hoebel, P. Rada, M. Kelly, M. A. Abou-Gharbia, J. E. Barrett, W. Childers, J. Pharmacol. Exp. Ther. 2005, 314, 1274-1289.
12. W. E. Childers Jr., B. L. Harrison, M. A. Abou-Gharbia, S. Raje, V. Parks, M. N. Pangalos, L. E. Schechter, Drugs Future 2007, 32, 399.
13. D. M. Bowen, A. W. Procter, D. M. A. Mann, J. S. Snowden, M. M. Esiri, D. Neary, P. T. Francis, Psychopharmacology 2008, 196, 603-610.
14. S. Sato, K. Mizukami, T. Asada, Int. J. Neuropsychopharmacol. 2007, 10, 281-283.
15. G. Becker, N. Streichenberger, T. Billard, A. Newman-Tancredi, L. Zimmer, CNS Neurosci. Ther. 2014, 20, 930-934.
16. M. Sato, T. Hirokawa, J. Chem. Inf. Model. 2014, 54, 3153-3161.
17. T. Klabunde, G. Hessler, ChemBioChem 2002, 3, 928-944.
18. B. C. Heng, D. Aubel, M. Fussenegger, Biotechnol. Adv. 2013, 31, 1676-1694.
19. A. Pau, G. Murineddu, B. Asproni, C. Murruzzu, G. E. Grella, G. A. Pinna, M. M. Curzu, I. Marchesi, L. Bagella, Molecules 2009, 14, 3494-3508.
20. G. Caliendo, V. Santagada, E. Perissutti, F. Fiorino, Curr. Med. Chem. 2005, 12, 1721-1753.
21. M. L. Lopez-Rodriguez, D. Ayala, B. Benhamu, M. J. Morcillo, A. Viso, Curr. Med. Chem. 2002, 9, 443-469.
22. H. W. Querfurth, F. M. LaFerla, N. Engl. J. Med. 2010, 362, 329-344.
23. Designing Multi-Target Drugs (Eds:, J. R. Morphy, C. J. Harris,), Royal Society of Chemistry, London, 2012.
24. C. Brühlmann, F. Ooms, P. A. Carrupt, B. Testa, M. Catto, F. Leonetti, C. Altomare, A. Carotti, J. Med. Chem. 2001, 44, 3195-3198.
25. L. Pisani, M. Catto, F. Leonetti, O. Nicolotti, A. Stefanachi, F. Campagna, A. Carotti, Curr. Med. Chem. 2011, 18, 4568-4587.
26. M. B. H Youdim, L. Kupershmidt, T. Amit, O. Weinreb, Parkins. Relat. Disord. 2014, 20, S 132-S 136.
27. K. Simone Tranches Dias, C. Viegas Jr., Curr. Neuropharmacol. 2014, 12, 239-255.
28. M. C. Carreiras, E. Mendes, M. J. Perry, A. P. Francisco, J. Marco-Contelles, Curr. Top. Med. Chem. 2013, 13, 1745-1770.
29. M. L. Bolognesi, M. Rosini, V. Andrisano, M. Bartolini, A. Minarini, V. Tumiatti, C. Melchiorre, Curr. Pharm. Des. 2009, 15, 601-613.
30. M. J. Matos, P. Janeiro, R. M. González Franco, S. Vilar, N. P. Tatonetti, L. Santana, E. Uriarte, F. Borges, J. A. Fontenla, D. Viña, Future Med. Chem. 2014, 6, 371-383.
31. N. Ye, Z. Song, A. Zhang, Curr. Med. Chem. 2014, 21, 437-457.
32. M. Takeda, I. Araki, T. Mochizuki, H. Nakagomi, H. Kobayashi, N. Sawada, H. Zakohji, J. Pharmacol. Sci. 2010, 112, 121-127.
33. P. Anand, B. Singh, Arch. Pharmacal Res. 2013, 36, 375-399.
34. N. H. Greig, T. Utsuki, Q.-S. Yu, X. Zhu, H. W. Holloway, T. A. Perry, B. Lee, D. H. Ingram, D. K. Lahiri, Curr. Med. Res. Opin. 2001, 17, 159-165.
35. H. Tanaka, S. Kirihara, H. Yasumatsu, T. Yakushiji, T. Nakao, Eur. J. Med. Chem. 1997, 32, 607-615.
36. S. Villa, G. Cignarella, M. M. Curzu, G. A. Pinna, E. Pini, L. Toma, J. Heterocycl. Chem. 1999, 36, 1253-1257.
37. G. A. Pinna, D. Barlocco, Eur. J. Med. Chem. 1991, 26, 787-790.
38. G. L. Ellman, K. D. Courtney, V. Andres Jr., R. M. A. Featherstone, Biochem. Pharmacol. 1961, 7, 88-90.
39. P. Taylor, J. Lwebuga-Mukasa, S. Lappi, J. Rademacher, Mol. Pharmacol. 1974, 10, 703-708.
40. D. Barlocco, G. Cignarella, F. Fanelli, B. Vitalis, P. Matyus, P. G. De Benedetti, Drug Des. Discovery 1997, 14, 273-290.
41. M. Leopoldo, F. Berardi, N. A. Colabufo, M. Contino, E. Lacivita, M. Niso, P. Perrone, V. Tortorella, J. Med. Chem. 2004, 47, 6616-6624.
42. F. Fiorino, B. Severino, F. De Angelis, E. Perissutti, E. Magli, F. Frecentese, A. Esposito, P. Massarelli, C. Nencini, V. Santagada, G. Caliendo, Bioorg. Med. Chem. Lett. 2010, 20, 2978-2982.
43. N. Denora, T. Cassano, V. Laquintana, A. Lopalco, A. Trapani, C. S. Cimmino, L. Laconca, A. Giuffrida, G. Trapani, Int. J. Pharm. 2012, 437, 221-231.
44. J. G. Baker, S. J. Hill, Trends Pharmacol. Sci. 2007, 28, 374-381.
45. C. Lecoutey, D. Hedou, T. Freret, P. Giannoni, F. Gaven, M. Since, V. Bouet, C. Ballandonne, S. Corvaisier, A. Malzert Fréon, S. Mignani, T. Cresteil, M. Boulouard, S. Claeysen, C. Rochais, P. Dallemagne, Proc. Natl. Acad. Sci. USA 2014, 111, E 3825-E 3830.
46. C. Mayama, M. Araie, Japan J. Ophthalmol. 2013, 57, 133-149.
47. P. Leff, I. G. Dougall, Trends Pharmacol. Sci. 1993, 14, 110-112.