Synthesis, structure, and neuroprotective properties of novel imidazolyl nitrones

Journal of Medicinal Chemistry

Volumn 43, Issue 11, 2000, Pages 2165-2175

  Dhainaut, Alain ^a   Tizot, André ^a   Raimbaud, Eric ^a   Lockhart, Brian ^b   Lestage, Pierre ^b   Goldstein, Solo ^a  

^a INSTITUT DE RECHERCHES SERVIER   (France)

^b INSTITUT DE RECHERCHES SERVIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

N TERT BUTYL ALPHA PHENYLNITRONE; NITRONE DERIVATIVE; TERT BUTYL HYDROPEROXIDE;

ANIMAL MODEL; ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; HYPOTHERMIA; MOUSE; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RAT;

ANIMALS; BLOOD-BRAIN BARRIER; BODY TEMPERATURE; IMIDAZOLES; MALE; MICE; NEUROPROTECTIVE AGENTS; NITROGEN OXIDES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034213307     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991154w     Document Type: Article

References (31)

1. (a) Chen, Q.; Fischer, A.; Reagan, J. D.; Yan, L. J.; Ames, B. N. Oxidative DNA Damage and Senescence of Human Diploid Fibroblast Cells. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 4337-4341.
2. (b) Ogilve, A. C.; Goeneveld, A. B. J.; Straub, J. P.; Thigs, L. G. Plasma Lipid Peroxides and Antioxidants in Human Septic Shock. Intensive Care Med. 1991, 17, 40-44.
3. Floyd, R. A. Role of Oxygen Free Radicals in Carcinogenesis and Brain Ischemia. FASEB J. 1990, 4, 2587-2597.
4. Hensley, K.; Pye, Q. N.; Tabatabaie, T.; Stewart, C. A.; Floyd, R. A. Reactive Oxygen Involvement in Neurodegenerative Pathways. In Neuroinflammation: Mechanism and Management, P. L. Woods, Eds.; Humana Press Inc.: Totowa, NJ, 1998; pp 265-276.
5. Floyd, R. A. The Protective Action of Nitrone Based Free Radical Traps in Neurodegenerative Disease. In Neurodegenerative Diseases, Fiskum, G.; Eds; Plenum Press: New York, 1996; pp 235-243.
6. Yuan, T. L.; Gu, J. L.; Lysko, P. G.; Cheng, H. Y., Barone, F. C.; Feurstein, G. Neuroprotective Effects of Phenyl-tert-butyl-nitrone in Gerbil Global Brain Ischemia and in Cultured Rat Cerebellar Neurons. Brain Res. 1992, 574, 193-197.
7. Floyd, R. A. Protective Action of Nitrone-Based Free Radical Traps against oxidative Damage to the Central Nervous Systems. Advances in Pharmacology, Academic Press Inc.: New York, 1997; Vol. 38, pp 361-378 and references therein.
8. Cheng, H. Y.; Liu, T.; Feurstein, G.; Barone, F. C. Distribution of Spin-Trapping Compounds in Rat Blood and Brain: In Vivo Microdialysis Determination. Free Radical Biol. Med. 1993, 14, 243-250.
9. French, J. F.; Thomas, C. E.; Downs, T. R.; Ohlweiler, D. F.; Carr, A. A.; Dage, R. C. Protective Effects of a Cyclic Nitrone Antioxidant in Animal Models of Endotoxic Shock. Bacteria Circulatory Shock 1994, 43, 130-136.
10. Hensley, K.; Carney, J. M.; Stewart, C. A.; Tabatabaie, T.; Pye, Q.; Floyd, R. A. Nitrone-Based Free Radical Traps as Neuroprotective Agents in Cerebral Ischemia and Other Pathologies. Neuroprotective Agents and Cerebral Ischemia; Academic Press Ltd.: New York, 1997; Chapter 13, pp 299-312.
11. (a) Fevig, T. L.; Bowen, S. M.; Janowick, D. A.; Jones, B. K.; Munson, H. R.; Ohlweiler, D. F.; Craig, E. T. Design, Synthesis and in Vitro Evaluation of Cyclic Nitrones as Free Radical Traps for the Treatment of Stroke. J. Med. Chem. 1996, 39, 4988-4996.
12. (b) Thomas, C. E.; Bernardelli, P.; Bowen, S. M.; Chaney, S. F.; Friedrich, D.; Janowick, D. A.; Jones, B. K.; Keeley, F. J.; Kehne, J. H.; Ketteler, B.; Ohlweiler, D. F.; Paquette, L. A.; Robke, D. J.; Fexig, T. L. Cyclic Nitrone Free Radical Traps: Isolation, Identification and Synthesis of 3,3-Dimethyl-3,4-dihydroisoquinolin-4-ol N-Oxide, a Metabolite with Reduced Side Effects. J. Med. Chem 1996, 39, 4997-5004.
13. Goldstein, S.; Dhainaut, A.; Tizot, A.; Lockhart, B.; Lestage, P. Nouveaux dérivés de nitrones, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. EP no 99/ 0967207, ADIR et Compagnie, 92415 Courbevoie France.
14. AM1 semiempirical and ab initio HF/3-21G* calculations (see also Experimental Section ).
15. Fleming, I. Frontier Orbitals and Organic Chemical Reactions; John Wiley & Sons: Chichester, 1976, pp 182-191.
16. Ikeda, K.; Tatsuno, T.; Ogo, H.; Masumoto, S.; Fujibayashi, T.; Nagata, R.; Makamura, T. Treating Neuro-Degenerative Diseases Using New or Known Nitrone or Amine Derivative Substituted by Aryl or Heteroaryl Group. WO 98/13332, Sumimoto Pharmaceuticals Co., Ltd 2-8 Osaka, Japan.
17. Ter Laak, A. M.; Tsai, R. S.; Donué-Op den Kelder, G. M.; Carrupt, P. A.; Testa, B. Lipophilicity and Hydrogen Bond Capacity of H1-Antihistaminic Agents in Relation to their Central Sedative Side Effects. Eur. J. Pharm. Sci. 1994, 2, 373-384.
18. Baldwin, J. J.; Kasinger, P. A.; Novello, F. C.; Spragne, J. M. 4-Trifluoromethylimidazoles and 5-(4-pyridyl)-1,2,4-triazoles, New Classes of Xanthine Oxidase Inhibitors. J. Med. Chem. 1975, 18, 895-900.
19. (a) Matthews, D. P.; Whitten, J. P.; McCarthy, J. R. A Convenient Procedure for the Preparation of 4(5)Cyanoimidazoles. J. Org. Chem. 1986, 51, 3228-3231.
20. (b) Matthews, D. P.; McCarthy, J. R.; Whitten, J. P.; Kastner, P. R.; Barney, C. L.; Marshall, F. N.; Ertel, M. A.; Burkhard, T.; Shea, P. J.; Kariya, T. Synthesis and Cardiotonic Activity of Novel Biimidazoles. J. Med. Chem. 1990, 33, 317-327.
21. (a) Nahm, S.; Weinreb, S. M. N-Methoxy-N-methylamides as Effective Acylating Agents. Tetrahedron Lett. 1981, 22, 3815-3818.
22. (b) Knorr, R.; Trzeciak, A.; Bannwarth, W.; Gillessen, D. New Coupling Reagents in Peptide Chemistry. Tetrahedron Lett. 1989, 30, 1927-1930.
23. Kenneth, L. 4-Lithio-1-Tritylimidazole as a Synthetic Intermediate. Synthesis of Imidazole-4-Carboxaldehyde. J. Heterocycl. Chem. 1985, 22, 57-59.
24. Lissel, M.; Schmidt, S.; Neumann, B. Dimethylcarbonat als Methylierunfsmittel unter Transfer-Katalytischen Bedingungen. Synthesis 1986, 5, 382-383.
25. (a) Adams, J. D.; Wang, B.; Klaidman, L. K.; Lebel, C. P.; Odunze, I. N.; Shah, D. New Aspects of Brain Oxidative Stress Induced by tert-Butylhydroperoxide. Free Radical Biol. Med. 1993, 15, 195-202.
26. (b) Adams, J. D.; Klaidman, L. K.; Huang, Y. M.; Cheng, J. J.; Wang, Z. J.; Nguyen, M.; Knusel, B.; Kuda, A. The Neuropathology of Intracerebroventricular tert-Butylhydroperoxide. Mol. Chem. Neuropathol. 1991, 26, 95-106.
27. (a) Tripos Inc., 1699 South Hanley Road, Saint-Louis, MO 63144-2913.
28. (b) Dewar, M. J. S.; Zoebish, E. G.; Healy; E. F.; Stewart, J. P. AM1: A New General Purpose Quantum Mechanical Molecular Model. J. Am. Chem. Soc., 1985, 107, 3902-3909.
29. (c) Gaussian 92/DFT, Revision F.3, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.; Johnson, B. G.; Wong, M. W.; Foresman, J. B.; Robb, M. A.; Head-Gordon, M.; Replogle, E. S.; Gomperts, R.; Andreas, J. L.; Raghavachari, K.; Binkley, J. S.; Gonzalez, C.; Martin, R. L.; Fox, D. J.; Defrees, D. J.; Baker, J.; Stewart, J. J. P.; Pople, J. A. Gaussian, Inc., Pittsburgh, PA, 1993.
30. oct from Structure. Chem. Rev. 1993, 93, 1281-1306.
31. (b) ClogP, version 4.51, Daylight Software, Daylight Chemical Information System, Inc., 441 Greg Ave., Santa Fe, NM 87501.