Furoxans (1,2,5-Oxadiazole- N -oxides) as novel no mimetic neuroprotective and procognitive agents

Journal of Medicinal Chemistry

Volumn 55, Issue 7, 2012, Pages 3076-3087

  Schiefer, Isaac T ^a   Vandevrede, Lawren ^a   Fa', Mauro ^b   Arancio, Ottavio ^b   Thatcher, Gregory R J ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b NewYork Presbyterian Hospital   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,5 OXADIAZOLE N OXIDE DERIVATIVE; 1H 1,2,4 OXADIAZOLO[4,3 A]QUINOXALIN 1 ONE; 3 (AMINOMETHYL) 4 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 (AMINOMETHYL) 4 PHENYL 1,2,5 OXADIAZOLE 2 OXIDE; 3 (AZIDOMETHYL) 4 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 (AZIDOMETHYL) 4 (4 NITROPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 (AZIDOMETHYL) 4 PHENYL 1,2,5 OXADIAZOLE 2 OXIDE; 3 (HYDROXYMETHYL) 4 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 (HYDROXYMETHYL) 4 (4 NITROPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 (HYDROXYMETHYL) 4 PHENYL 1,2,5 OXADIAZOLE 2 OXIDE; 3 [[4 (3 AMINOPHENYL) 1H 1,2,3 TRIAZOL 1 YL]METHYL] 4 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 [[4 [(2,8 DIMETHYL 3,4 DIHYDRO 1H PYRIDO[4,3 B]INDOL 5(2H) YL)METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 4 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 [[4 [[2 (4 FLUOROPHENYLSULFONAMIDO) 3 METHYLBUTANAMIDO]METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 4 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 [[4 [[2 (4 FLUOROPHENYLSULFONAMIDO) 3 METHYLBUTANAMIDO]METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 4 (4 NITROPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 3 [[4 [[2 (4 FLUOROPHENYLSULFONAMIDO) 3 METHYLBUTANAMIDO]METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 4 PHENYL 1,2,5 OXADIAZOLE 2 OXIDE; 3 [[4 METHYL 2 (PHENYLSULFONAMIDO)PENTANAMIDO]METHYL] 4 PHENYL 1,2,5 OXADIAZOLE 2 OXIDE; 4 (4 METHOXYPHENYL) 3 [[4 METHYL 2 (PHENYLSULFONAMIDO)PENTANAMIDO]METHYL] 1,2,5 OXADIAZOLE 2 OXIDE; 4 [[4 [[2 (4 FLUOROPHENYLSULFONAMIDO) 3 METHYLBUTANAMIDO]METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 3 (4 METHOXYPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 4 [[4 [[2 (4 FLUOROPHENYLSULFONAMIDO) 3 METHYLBUTANAMIDO]METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 3 (4 NITROPHENYL) 1,2,5 OXADIAZOLE 2 OXIDE; 4 [[4 [[2 (4 FLUOROPHENYLSULFONAMIDO) 3 METHYLBUTANAMIDO]METHYL] 1H 1,2,3 TRIAZOL 1 YL]METHYL] 3 PHENYL 1,2,5 OXADIAZOLE 2 OXIDE; 4 METHYL N [(4 PHENYL 1,2,5 OXADIAZOL 3 YL)METHYL] 2 (PHENYLSULFONAMIDO)PENTANAMIDE; 4 PHENYL 3 [(4 PHENYL 1H 1,2,3 TRIAZOL 1 YL)METHYL] 1,2,5 OXADIAZOLE 2 OXIDE; AMYLOID BETA PROTEIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; GUANYLATE CYCLASE; NEUROPROTECTIVE AGENT; NITRIC OXIDE; NITROUS OXIDE; PEPTIDOMIMETIC AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL PROTECTION; CHEMICAL REACTION; COGNITION; CONTROLLED STUDY; CYTOTOXICITY; EMBRYO; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIPPOCAMPUS; LEARNING; LONG TERM POTENTIATION; MEMORY; NERVE CELL CULTURE; NEUROPROTECTION; NONHUMAN; RAT; SIGNAL TRANSDUCTION; SYNAPSE; TANDEM MASS SPECTROMETRY;

AMYLOID BETA-PEPTIDES; ANIMALS; CELLS, CULTURED; CRYSTALLOGRAPHY, X-RAY; CYSTEINE; GUANYLATE CYCLASE; HIPPOCAMPUS; LONG-TERM POTENTIATION; NEURONS; NEUROPROTECTIVE AGENTS; NITRIC OXIDE; NITRIC OXIDE DONORS; NOOTROPIC AGENTS; OXADIAZOLES; PEPTIDOMIMETICS; QUINOXALINES; RATS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; SIGNAL TRANSDUCTION; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SYNAPSES;

EID: 84859796244     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201504s     Document Type: Article

References (59)

1. Ghosh, P.; Ternai, B.; Whitehouse, M. Benzofurazans and benzofuroxans: biochemical and pharmacological properties Med. Res. Rev. 1981, 1, 159-187
2. Stuart, K. L. Furazans Heterocycles 1975, 3, 651-690
3. Cerecetto, H.; Gonzalez, M. Benzofuroxan and furoxan. Chemistry and biology Top. Heterocycl. Chem. 2007, 10, 265-308
4. Medana, C.; Ermondi, G.; Fruttero, R.; Di Stilo, A.; Ferretti, C.; Gasco, A. Furoxans as nitric oxide donors. 4-Phenyl-3-furoxancarbonitrile: thiol-mediated nitric oxide release and biological evaluation J. Med. Chem. 1994, 37, 4412-4416
5. Ghosh, P. B.; Whitehouse, M. W. Potential antileukemic and immunosuppressive drugs. Preparation and in vitro pharmacological acitivity of some benzo-2,1,3-oxadiazoles (benzofurazans) and their N -oxides (benzofuroxans) J. Med. Chem. 1968, 11, 305-311
6. Whitehouse, M. W.; Ghosh, P. B. 4-Nitrobenzofurazans and 4-nitrobenzofuroxans: a new class of thiol-neutralising agents and potent inhibitors of nucleic acid synthesis in leucocytes Biochem. Pharmacol. 1968, 17, 158-161
7. Ferioli, R.; Fazzini, A.; Folco, G. C.; Fruttero, R.; Calvino, R.; Gasco, A.; Bongrani, S.; Civelli, M. NO-mimetic furoxans: arylsulphonylfuroxans and related compounds Pharm. Res. 1993, 28, 203-212
8. Boschi, D.; Di Stilo, A.; Cena, C.; Lolli, M.; Fruttero, R.; Gasco, A. Studies on agents with mixed NO-dependent vasodilating and beta-blocking activities Pharm. Res. 1997, 14, 1750-1758
9. Boschi, D.; Tron, G. C.; Di Stilo, A.; Fruttero, R.; Gasco, A.; Poggesi, E.; Motta, G.; Leonardi, A. New potential uroselective NO-donor alpha1-antagonists J. Med. Chem. 2003, 46, 3762-3765
10. Buonsanti, M. F.; Bertinaria, M.; Di Stilo, A.; Cena, C.; Fruttero, R.; Gasco, A. Nitric Oxide Donor beta 2-Agonists: Furoxan Derivatives Containing the Fenoterol Moiety and Related Furazans J. Med. Chem. 2007, 50, 5003-5011
11. Cena, C.; Boschi, D.; Tron, G. C.; Chegaev, K.; Lazzarato, L.; Di Stilo, A.; Aragno, M.; Fruttero, R.; Gasco, A. Development of a new class of potential antiatherosclerosis agents: NO-donor antioxidants Bioorg. Med. Chem. Lett. 2004, 14, 5971-5974
12. Cena, C.; Lolli, M. L.; Lazzarato, L.; Guaita, E.; Morini, G.; Coruzzi, G.; McElroy, S. P.; Megson, I. L.; Fruttero, R.; Gasco, A. Antiinflammatory, gastrosparing, and antiplatelet properties of new NO-donor esters of aspirin J. Med. Chem. 2003, 46, 747-754
13. Chegaev, K.; Cena, C.; Giorgis, M.; Rolando, B.; Tosco, P.; Bertinaria, M.; Fruttero, R.; Carrupt, P.-A.; Gasco, A. Edaravone Derivatives Containing NO-Donor Functions J. Med. Chem. 2009, 52, 574-578
14. Sorba, G.; Galli, U.; Cena, C.; Fruttero, R.; Gasco, A.; Morini, G.; Adami, M.; Coruzzi, G.; Brenciaglia, M. I.; Dubini, F. A new furoxan NO-donor rabeprazole derivative and related compounds ChemBioChem 2003, 4, 899-903
15. Tosco, P.; Bertinaria, M.; Di Stilo, A.; Cena, C.; Sorba, G.; Fruttero, R.; Gasco, A. Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related furazan derivatives Bioorg. Med. Chem. 2005, 13, 4750-4759
16. Velazquez, C.; Rao, P. N.; McDonald, R.; Knaus, E. E. Synthesis and biological evaluation of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides and 3,4-diphenyl-1,2,5-oxadiazoles as potential hybrid COX-2 inhibitor/nitric oxide donor agents Bioorg. Med. Chem. 2005, 13, 2749-2757
17. Buonsanti, M. F.; Bertinaria, M.; Stilo, A. D.; Cena, C.; Fruttero, R.; Gasco, A. Nitric oxide donor beta2-agonists: furoxan derivatives containing the fenoterol moiety and related furazans J. Med. Chem. 2007, 50, 5003-5011
18. Boiani, L.; Aguirre, G.; Gonzalez, M.; Cerecetto, H.; Chidichimo, A.; Cazzulo, J. J.; Bertinaria, M.; Guglielmo, S. Furoxan-, alkylnitrate-derivatives and related compounds as anti-trypanosomatid agents: mechanism of action studies Bioorg. Med. Chem. 2008, 16, 7900-7907
19. Boiani, M.; Cerecetto, H.; Gonzalez, M.; Risso, M.; Olea-Azar, C.; Piro, O. E.; Castellano, E. E.; Lopez de Cerain, A.; Ezpeleta, O.; Monge-Vega, A. 1,2,5-Oxadiazole N -oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV Eur. J. Med. Chem. 2001, 36, 771-782
20. Thatcher, G. R. J.; Nicolescu, A. C.; Bennett, B. M.; Toader, V. Nitrates and NO release: contemporary aspects in biological and medicinal chemistry Free Radical Biol. Med. 2004, 37, 1122-1143
21. Thatcher, G. R. J.; Bennett, B. M.; Reynolds, J. N. NO chimeras as therapeutic agents in Alzheimer's disease Curr. Alzheimer Res. 2006, 3, 237-245
22. Zhuo, M.; Hu, Y.; Schultz, C.; Kandel, E. R.; Hawkins, R. D. Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation Nature 1994, 368, 635-639
23. Lu, Y. F.; Kandel, E. R.; Hawkins, R. D. Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus J. Neurosci. 1999, 19, 10250-10261
24. Bon, C. L.; Garthwaite, J. On the role of nitric oxide in hippocampal long-term potentiation J. Neurosci. 2003, 23, 1941-1948
25. Haley, J. E.; Wilcox, G. L.; Chapman, P. F. The role of nitric oxide in hippocampal long-term potentiation Neuron 1992, 8, 211-216
26. Arancio, O.; Kiebler, M.; Lee, C. J.; Lev-Ram, V.; Tsien, R. Y.; Kandel, E. R.; Hawkins, R. D. Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons Cell 1996, 87, 1025-1035
27. Mohr, S.; Zech, B.; Lapetina, E. G.; Brune, B. Inhibition of caspase-3 by S -nitrosation and oxidation caused by nitric oxide Biochem. Biophys. Res. Commun. 1997, 238, 387-391
28. Puzzo, D.; Vitolo, O.; Trinchese, F.; Jacob, J. P.; Palmeri, A.; Arancio, O. Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP- responsive element-binding protein pathway during hippocampal synaptic plasticity J. Neurosci. 2005, 25, 6887-6897
29. Lipton, S. A.; Choi, Y. B.; Pan, Z. H.; Lei, S. Z.; Chen, H. S.; Sucher, N. J.; Loscalzo, J.; Singel, D. J.; Stamler, J. S. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds Nature 1993, 364, 626-632
30. Thatcher, G. R. J. An introduction to NO-related therapeutic agents Curr. Top. Med. Chem. 2005, 5, 597-601
31. Smith, S.; Dringenberg, H. C.; Bennett, B. M.; Thatcher, G. R. J.; Reynolds, J. N. A novel nitrate ester reverses the cognitive impairment caused by scopolamine in the Morris water maze Neuroreport 2000, 11, 3883-3886
32. Reynolds, J. N.; Bennett, B. M.; Boegman, R. J.; Jhamandas, K.; Ratz, J. D.; Zavorin, S. I.; Scutaru, D.; Dumitrascu, A.; Thatcher, G. R. J. Neuroprotection against ischemic brain injury conferred by a novel nitrate ester Bioorg. Med. Chem. Lett. 2002, 12, 2863-2866
33. Vitolo, O. V.; Sant'Angelo, A.; Costanzo, V.; Battaglia, F.; Arancio, O.; Shelanski, M. Amyloid beta -peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 13217-13221
34. Puzzo, D.; Staniszewski, A.; Deng, S. X.; Privitera, L.; Leznik, E.; Liu, S.; Zhang, H.; Feng, Y.; Palmeri, A.; Landry, D. W.; Arancio, O. Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid-beta load in an Alzheimer's disease mouse model J. Neurosci. 2009, 29, 8075-8086
35. Blurton-Jones, M.; Kitazawa, M.; Martinez-Coria, H.; Castello, N. A.; MuIller, F.-J.; Loring, J. F.; Yamasaki, T. R.; Poon, W. W.; Green, K. N.; LaFerla, F. M. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 13594-13599
36. Peng, S.; Wuu, J.; Mufson, E. J.; Fahnestock, M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease J. Neurochem. 2005, 93, 1412-1421
37. Puzzo, D.; Palmeri, A.; Arancio, O. Involvement of the nitric oxide pathway in synaptic dysfunction following amyloid elevation in Alzheimer's disease Rev. Neurosci. 2006, 17, 497-523
38. Hook, V.; Kindy, M.; Hook, G. Cysteine protease inhibitors effectively reduce in vivo levels of brain beta-amyloid related to Alzheimer's disease Biol. Chem. 2007, 388, 247-252
39. Trinchese, F.; Fa, M.; Liu, S.; Zhang, H.; Hidalgo, A.; Schmidt, S. D.; Yamaguchi, H.; Yoshii, N.; Mathews, P. M.; Nixon, R. A.; Arancio, O. Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease J. Clin. Invest. 2008, 118, 2796-2807
40. Balicki, R.; Cybulski, M.; Maciejewski, G. An Efficient Deoxygenation of Heteroaromatic N -Oxides Using Zinc Dust/Ammonium Formate Reagent System Synth. Commun. 2003, 33, 4137-4141
41. Medana, C.; Di Stilo, A.; Visentin, S.; Fruttero, R.; Gasco, A.; Ghigo, D.; Bosia, A. NO donor and biological properties of different benzofuroxans Pharm. Res. 1999, 16, 956-960
42. Sako, M.; Oda, S.; Ohara, S.; Hirota, K.; Maki, Y. J. Org. Chem. 1998, 63, 6947
43. Feelisch, M.; SchoInafingeri, K.; Noack, H. Thiol-mediated generation of nitric oxide accounts for the vasodilator action of furoxans Biochem. Pharmacol. 1992, 44, 1149-1157
44. Sorba, G.; Medana, C.; Fruttero, R.; Cena, C.; Di Stilo, A.; Galli, U.; Gasco, A. Water soluble furoxan derivatives as NO prodrugs J. Med. Chem. 1997, 40, 463-469
45. Ferioli, R.; Folco, G. C.; Ferretti, C.; Gasco, A. M.; Medana, C.; Fruttero, R.; Civelli, M.; Gasco, A. A new class of furoxan derivatives as NO donors: mechanism of action and biological activity Br. J. Pharmacol. 1995, 114, 816-820
46. Rai, G.; Sayed, A. A.; Lea, W. A.; Luecke, H. F.; Chakrapani, H.; Prast-Nielsen, S.; Jadhav, A.; Leister, W.; Shen, M.; Inglese, J.; Austin, C. P.; Keefer, L.; Arner, E. S.; Simeonov, A.; Maloney, D. J.; Williams, D. L.; Thomas, C. J. Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis J. Med. Chem. 2009, 52, 6474-6483
47. Boiani, M.; Cerecetto, H.; González, M.; Risso, M.; Olea-Azar, C.; Piro, O. E.; Castellano, E. E.; López de Ceráin, A.; Ezpeleta, O.; Monge-Vega, A. 1,2,5-Oxadiazole N -oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV Eur. J. Med. Chem. 2001, 36, 771-782
48. Melino, G.; Bernassola, F.; Knight, R. A.; Corasaniti, M. T.; Nistic, G.; Finazzi-Agr, A. S-nitrosylation regulates apoptosis Nature 1997, 388, 432-433
49. Ascenzi, P.; Bocedi, A.; Gentile, M.; Visca, P.; Gradoni, L. Inactivation of parasite cysteine proteinases by the NO-donor 4-(phenylsulfonyl)-3-((2- (dimethylamino)ethyl)thio)-furoxan oxalate Biochim. Biophys. Acta 2004, 1703, 69-77
50. Ascenzi, P.; Salvati, L.; Bolognesi, M.; Colasanti, M.; Polticelli, F.; Venturini, G. Inhibition of cysteine protease activity by NO-donors Curr. Protein Pept. Sci. 2001, 2, 137-153
51. Loo, D. T.; Rillema, J. R.; Jennie, P. M.; David, B. Measurement of Cell Death. Methods in Cell Biology; Academic Press: New York, 1998; Vol. 57, Chapter 14, pp 251-264.
52. Goldberg, M. P.; Strasser, U.; Dugan, L. L. Techniques for assessing neuroprotective drugs in vitro Int. Rev. Neurobiol. 1997, 40, 69-93
53. Lee, K. S.; Frank, S.; Vanderklish, P.; Arai, A.; Lynch, G. Inhibition of proteolysis protects hippocampal neurons from ischemia Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7233-7237
54. Rami, A.; Krieglstein, J. Protective effects of calpain inhibitors against neuronal damage caused by cytotoxic hypoxia in vitro and ischemia in vivo Brain Res. 1993, 609, 67-70
55. Komatsu, K.; Inazuki, K.; Hosoya, J.; Satoh, S. Beneficial effect of new thiol protease inhibitors, epoxide derivatives, on dystrophic mice Exp. Neurol. 1986, 91, 23-29
56. Kandel, E. R. The molecular biology of memory storage: a dialogue between genes and synapses Science 2001, 294, 1030-1038
57. Lambert, M. P.; Barlow, A. K.; Chromy, B. A.; Edwards, C.; Freed, R.; Liosatos, M.; Morgan, T. E.; Rozovsky, I.; Trommer, B.; Viola, K. L.; Wals, P.; Zhang, C.; Finch, C. E.; Krafft, G. A.; Klein, W. L. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 6448-6453
58. Arancio, O.; Kiebler, M.; Lee, C. J.; Lev-Ram, V.; Tsien, R. Y.; Kandel, E. R.; Hawkins, R. D. Nitric Oxide Acts Directly in the Presynaptic Neuron to Produce Long-Term Potentiation in Cultured Hippocampal Neurons Cell 1996, 87, 1025-1035
59. Brewer, G. J.; Torricelli, J. R.; Evege, E. K.; Price, P. J. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination J. Neurosci. Res. 1993, 35, 567-576