Synthesis and biological evaluation of the 1-arylpyrazole class of σ1 receptor antagonists: Identification of 4-{2-[5-methyl-1- (naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862)

Journal of Medicinal Chemistry

Volumn 55, Issue 19, 2012, Pages 8211-8224

  Díaz, José Luis ^a   Cuberes, Rosa ^a   Berrocal, Joana ^a   Contijoch, Montserrat ^a   Christmann, Ute ^a   Fernández, Ariadna ^a   Port, Adriana ^a   Holenz, Jörg ^a   Buschmann, Helmut ^a   Laggner, Christian ^b   Serafini, Maria Teresa ^a   Burgueño, Javier ^a   Zamanillo, Daniel ^a   Merlos, Manuel ^a   Vela, José Miguel ^a   Almansa, Carmen ^a  

^a Drug Discovery and Preclinical Development   (Spain)

^b UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 [5 METHYL 1 (NAPHTHALEN 2 YL) 1H PYRAZOL 3 YLOXY]ETHYL]MORPHOLINE; ANALGESIC AGENT; CAPSAICIN; PREGABALIN; PYRAZOLE DERIVATIVE; SIGMA 1 OPIATE RECEPTOR; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; HUMAN; HUMAN CELL; LIVER MICROSOME; MALE; MOUSE; NERVE LIGATION; NEUROPATHIC PAIN; NONHUMAN; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BRAIN; FEMALE; GUINEA PIGS; HEK293 CELLS; HUMANS; HYPERALGESIA; MALE; MICE; MICROSOMES, LIVER; MORPHOLINES; MOTOR ACTIVITY; NEURALGIA; PATCH-CLAMP TECHNIQUES; PYRAZOLES; RADIOLIGAND ASSAY; RECEPTORS, SIGMA; SCIATIC NEUROPATHY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84867387612     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm3007323     Document Type: Article

References (50)

1. Quirion, R.; Bowen, W. D.; Itzhak, Y.; Junien, J. L.; Musacchio, J. M.; Rothman, R. B.; Su, T. P.; Tam, S. W.; Taylor, D. P. A proposal for the classification of sigma binding sites Trends Pharmacol. Sci. 1992, 13, 85-86
2. 1-binding site Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 8072-8077
3. Kekuda, R.; Prasad, P. D.; Fei, Y. J.; Leibach, F. H.; Ganapathy, V. Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1) Biochem. Biophys. Res. Commun. 1996, 229, 553-558
4. Su, T. P.; Hayashi, T.; Maurice, T.; Buch, S.; Ruoho, A. E. The sigma-1 receptor chaperone as an inter-organelle signalling modulator Trends Pharmacol. Sci. 2010, 31, 557-566
5. Monnet, F. P.; Debonnel, G.; Junien, J. L.; De Montigny, C. N -Methyl- d -aspartate-induced neuronal activation is selectively modulated by sigma receptors Eur. J. Pharmacol. 1990, 179, 441-445
6. Cheng, Z. X.; Lan, D. M.; Wu, P. Y.; Zhu, Y. H.; Dong, Y.; Ma, L.; Zheng, P. Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors Exp. Neurol. 2010, 210, 128-136
7. Chien, C. C.; Pasternak, G. W. Selective antagonism of opioid analgesia by a sigma system J. Pharmacol. Exp. Ther. 1994, 271, 1583-1590
8. Kim, F. J.; Kovalyshyn, I.; Burgman, M.; Neilan, C.; Chien, C. C.; Pasternak, G. W. Sigma-1 receptor modulation of G-protein-coupled receptor signaling: potentiation of opioid transduction independent from receptor binding Mol. Pharmacol. 2010, 77, 695-703
9. Zamanillo, D.; Portillo-Salido, E; Vela, J. M.; Romero, L. Sigma 1 Receptor Chaperone: Pharmacology and Therapeutic Perspectives. In Therapeutic Targets; Botana, J. M.; Loza, M.; Eds.; John Wiley & Sons: Hoboken, NJ, 2012; Chapter 6, pp 225-278.
10. Maurice, T.; Su, T. P. The pharmacology of sigma-1 receptors Pharmacol. Ther. 2009, 124, 195-206
11. Marrazzo, A.; Cobos, E. J.; Parenti, C.; Arico, G.; Marrazzo, G.; Ronsisvalle, S.; Pasquinucci, L.; Prezzavento, O.; Colabufo, N. A.; Contino, M. A.; Gonzalez, L. G.; Scoto, M. G.; Ronsisvalle, G. Novel potent and selective sigma ligands: evaluations of their agonist and antagonist properties J. Med. Chem. 2011, 54, 3669-3673
12. Crawford, K. W.; Bowen, W. D. Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines Cancer Res. 2002, 1, 313-322
13. Cendán, C. M.; Pujalte, J. M.; Portillo-Salido, E.; Montoliu, L.; Baeyens, J. M. Formalin-induced pain is reduced in sigma(1) receptor knockout mice Eur. J. Pharmacol. 2005, 511, 73-74
14. Entrena, J. M.; Cobos, E. J.; Nieto, F. R.; Cendán, C. M.; Gris, G.; Del Pozo, E.; Zamanillo, D.; Baeyens, J. M. Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice Pain 2009, 143, 252-261
15. De la Puente, B.; Nadal, X.; Portillo-Salido, E.; Sánchez-Arroyos, R.; Ovalle, S.; Palacios, G.; Muro, A.; Romero, L.; Entrena, J. M.; Baeyens, J. M; López-García, J. A.; Maldonado, R.; Zamanillo, D.; Vela, J. M. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury Pain 2009, 145, 294-303
16. Cendán, C. M.; Pujalte, J. M.; Portillo-Salido, E.; Baeyens, J. M. Antinociceptive effects of haloperidol and its metabolites in the formalin test in mice Psychopharmacology (Berlin) 2005, 182, 485-493
17. Roh, D. H.; Kim, H. W.; Yoon, S. Y.; Seo, H. S.; Kwon, Y. B.; Kim, K. W.; Han, H. J.; Beitz, A. J.; Na, H. S.; Lee, J. H. Intrathecal injection of the sigma 1 receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain Anesthesiology 2008, 109, 879-889
18. Drews, E.; Zimmer, A. Central sensitization needs sigma receptors Pain 2009, 145, 269-270
19. Díaz, J. L.; Zamanillo, D.; Corbera, J.; Baeyens, J. M.; Maldonado, R.; Pericàs, M. A.; Vela, J. M.; Torrens, A. Selective sigma-1 receptor antagonists: emerging target for the treatment of neuropathic pain Cent. Nerv. Syst. Agents Med. Chem. 2009, 9, 172-183
20. Romero, L.; Zamanillo, D.; Nadal, X.; Sánchez-Arroyos, R.; Rivera-Arconada, I.; Dordal, A.; Montero, A.; Muro, A.; Bura, A.; Segalés, C.; Laloya, M.; Hernández, E.; Portillo-Salido, E.; Escriche, M.; Codony, X.; Encina, G.; Burgueño, J.; Merlos, M.; Baeyens, J. M.; Giraldo, J.; López-García, J. A.; Maldonado, R.; Plata-Salamán, C. R.; Vela, J. M. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization. Br. J. Pharmacol. [Online early access]. DOI: 10.1111/j.1476-5381.2012.01942.x. Published Online: Mar 9, 2012.
21. Abadias, M.; Escriche, M.; Vaqué, A.; Sust, M.; Encina, G. Safety, tolerability and pharmacokinetics of single and multiple doses of a novel sigma-1 receptor antagonist in three randomized phase I studies. Br. J. Clin. Pharmacol. [Online early access]. DOI: 10.1111/j.1365-2125.2012.04333.x. Published Online: May 21, 2012.
22. Laggner, C.; Cuberes, R.; Holenz, J.; Berrocal, J.; Contijoch, M. PCT Pat. Appl. WO2006/021462, 2006.
23. Cuberes, R.; Holenz, J. PCT Pat. Appl. WO2007/098963, 2007.
24. Cuberes, R.; Holenz, J. PCT Pat. Appl. WO2007/098964, 2007.
25. Cuberes, R.; Holenz, J. PCT Pat. Appl. WO2007/098967, 2007.
26. Gaede, B. J.; McDermott, L. L. Novel perfluoroalkyl-substituted pyrazoles. 1. Hydroxypyrazoles J. Heterocycl. Chem. 1993, 30, 49-54
27. Koenig, H.; Goetz, N.; Kirstgen, R.; Mueller, B.; Oberdorf, K. Eur. Pat. Appl. EP680954, 1995.
28. Doria, G.; Passarotti, C.; Sala, R.; Magrini, R.; Sberze, P.; Tibolla, M.; Ceserani, R.; Castello, R. Synthesis and antiulcer activity of (E)-5-[2-(3-pyridyl)ethenyl]-1 H,7 H -pyrazolo[1,5- a ]pyrimidine-7-ones Farmaco 1986, 41, 417-429
29. Rossiter, S.; Woo, C. K.; Hartzoulakis, B.; Wishart, G.; Stanyer, L.; Labadie, J. W.; Selwood, D. L. Copper(II)-mediated arylation with aryl boronic acids for the N-derivatization of pyrazole libraries J. Comb. Chem. 2004, 6, 385-390
30. 1 receptor ligands with exocyclic amino moiety (increased distance 1) Bioorg. Med. Chem. 2011, 19, 3141-3151
31. 1 receptor binding J. Med. Chem. 1994, 37, 1214-1219
32. Laggner, C.; Schieferer, C.; Fiechtner, B.; Poles, G.; Hoffmann, R. D.; Glossmann, H.; Langer, T.; Moebius, E. F. Discovery of high-affinity ligands of σ1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening J. Med. Chem. 2005, 48, 4754-4764
33. 3H](+)pentazocine to recognition sites in guinea pig brain Eur. J. Pharmacol. 1992, 227, 371-378
34. Ronsisvalle, G.; Marrazzo, A.; Prezzavento, O.; Cagnotto, A.; Mennini, T.; Parenti, C.; Scoto, G. M. Opioid and sigma receptor studies. New developments in the design of selective sigma ligands Pur. Appl. Chem. 2001, 73, 1499-1509
35. Costa, B. R.; Radesca, L.; di Paolo, L.; Bowen, W. D. Synthesis, characterization, and biological evaluation of a novel class of N -(arylethyl)- N -alkyl-2-(1-pyrrolidinyl)ethylamines: structural requirements and binding affinity at the sigma receptor J. Med. Chem. 1992, 35, 38-47
36. Obach, R. S.; Baxter, J. G.; Liston, T. E.; Silber, B. M.; Jones, B. C.; MacIntyre, F.; Rance, D. J.; Wastall, P. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data J. Pharmacol. Exp. Ther. 1997, 283, 46-58
37. Obach, R. S. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: an examination of in vitro half-life approach and nonspecific binding to microsomes Am. Soc. Pharmacol. Exp. Ther. 1999, 27, 1350-1359
38. o J. Pharmacol. Toxicol. Methods 2004, 50, 187-199
39. Cobos, E. J.; Baeyens, J. M.; Del Pozo, E. Phenytoin differentially modulates the affinity of agonist and antagonist ligands for sigma 1 receptors of guinea pig brain Synapse 2005, 55, 192-195
40. Vidal-Torres, A.; Touriño, C.; Romero, L.; Baeyens, J. M.; Zamanillo, D.; Maldonado, R.; Vela, J. M. Potentiation of morphine analgesia but inhibition of the rewarding effects of morphine following co-administration of a new selective sigma-1 receptor antagonist Eur. J. Pain 2009, 3 (Suppl. 1) Abstract 341, S104
41. Gris, G.; Vidal, A.; Fort, M.; Aubel, B.; Romero, L.; González, A.; Portillo-Salido, E.; Baeyens, J. M.; Vela, J. M.; Deseure, K.; Zamanillo, D. Analgesic efficacy in rat models of experimental pain of a new selective sigma-1 receptor antagonist Eur. J. Pain 2009, 3 (Suppl. 1) Abstract 335, S102
42. Malmberg, A. B.; Basbaum, A. I. Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates Pain 1998, 76, 215-222
43. Wager, T. T.; Hou, X.; Verhoest, P. R.; Villalobos, A. Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties ACS Chem. Neurosci. 2010, 1, 435-449
44. Hu, M.; Ling, J.; Lin, H.; Chen, J. Use of Caco-2 Cell Monolayers To Study Drug Absorption and Metabolism. In Optimization in Drug Discovery: In Vitro Methods; Yan, Z.; Caldwell, G. W., Eds.; Humana Press, Totowa, NJ, 2004; pp 19-36.
45. Stresser, D. M. High-Throughput Screening of Human Cytochrome P450 Inhibitors Using Fluorometric Substrates. Methodology for 25 Enzyme/Substrate Pairs. In Optimization in Drug Discovery: In Vitro Methods; Yan, Z.; Caldwell, G. W., Eds.; Humana Press: Totowa, NJ, 2004; pp 215-230.
46. Yan, Z.; Caldwell, G. W. Evaluation of Cytochrome P450 Inhibition in Human Liver Microsomes. In Optimization in Drug Discovery: In Vitro Methods; Yan, Z.; Caldwell, G. W., Eds.; Humana Press: Totowa, NJ, 2004; pp 231-244
47. Drug Interaction Studies-Study Design, Data Analysis, Implications for Dosing and Labeling. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), September 2006, and February 2012.
48. Box, K. J.; Comer, E. A. Using measured pKa, logP and solubility to investigate supersaturation and predict BCS class Curr. Drug Metab. 2008, 9, 869-878
49. Di, L.; Kerns, E. H.; Hong, Y.; Kleintop, T. A.; McConnell, O. J.; Huryn, D. M. Optimization of a higher throughput microsomal stability screening assay for profiling drug discovery candidates J. Biomol. Screening 2003, 8, 453-462
50. Di, L.; Kerns, E. H.; Gao, N.; Li, S. Q.; Huang, Y.; Bourassa, J. L.; Huryn, D. M. Experimental design of single-time-point high-throughput microsomal stability assay J. Pharmacol. Sci. 2004, 93, 1537-1544