Synthesis and in vitro evaluation of new 8-amino-1,4-benzoxazine derivatives as neuroprotective antioxidants

Journal of Medicinal Chemistry

Volumn 42, Issue 24, 1999, Pages 5043-5052

  Largeron, Martine ^a   Lockhart, Brian ^b   Pfeiffer, Bruno ^c   Fleury, Maurice Bernard ^a  

^a UNIVERSITÉ PARIS DESCARTES   (France)

^b INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

^c ADIR   (France)

Author keywords

[No Author keywords available]

Indexed keywords

(3 TERT BUTYL 8 ISOPENTYLAMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (3 TERT BUTYL 8 PHENYLETHYLAMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (3,3 DIMETHYL 8 HYDROXYETHYLAMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (3,3 DIMETHYL 8 ISOPENTYLAMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (3,3 DIPHENYL 8 ISOPENTYLAMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (8 BENZYLAMINO 3 SPIRO 1' CYCLOPENTYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (8 BENZYLAMINO 3 TERT BUTYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (8 BENZYLAMINO 3,3 DIMETHYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (8 BENZYLAMINO 3,3 DIPHENYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; (8 ISOBUTYLAMINO 3 SPIRO 1' CYCLOPENTYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL)(PHENYL)METHANONE; [3 HYDROXYMETHYL 3 METHYL 8 (2 HYDROXYETHYLAMINO) 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL](PHENYL)METHANONE; [3 HYDROXYMETHYL 3 METHYL 8 [2 HYDROXY 1 (HYDROXYMETHYL)ETHYL]AMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL](PHENYL)METHANONE; [3,3 DIMETHYL 8 [2 HYDROXY 1 (HYDROXYMETHYL)ETHYL]AMINO 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL](PHENYL)METHANONE; [8 (2 HYDROXYETHYLAMINO 3,3 DIHYDROXYMETHYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL](PHENYL)METHANONE; [8 [2 HYDROXY 1 (HYDROXYMETHYL)ETHYL]AMINO 3 HYDROXYMETHYL 3,4 DIHYDRO 2H 1,4 BENZOXAZIN 5 YL](PHENYL)METHANONE; ANTIOXIDANT; NEUROPROTECTIVE AGENT; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CHEMICAL REACTION; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; MOUSE; NERVE CELL DEGENERATION; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIOXIDANTS; BENZOPHENONES; CELL DEATH; CELL LINE; HIPPOCAMPUS; MICE; MOLECULAR STRUCTURE; NERVE DEGENERATION; NEURONS; NEUROPROTECTIVE AGENTS; OXAZINES; OXIDATIVE STRESS; PSYCHOTROPIC DRUGS; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033518227     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991105j     Document Type: Article

References (29)

1. Chance, B.; Sies, H.; Boveris, A. Hydroperoxide metabolism mammalian organs. Physiol. Rev. 1979, 59, 527-605.
2. Imlay, J. A.; Chin, S. M.; Linn, S. Toxic DNA damage hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 1988, 240, 640-642.
3. Halliwell, B.; Gutteridge, J. M. C. Free radicals in Biology and Medicine, 3rd ed.; Oxford University Press: 1999; pp 246-350.
4. Porsolt, R. D.; Lenègre, A.; Avril, L; Stéru, L.; Doumont, G. The effects of exifone, a new agent for senile memory disorder, on two models of memory in the mouse. Pharmacol. Biochem. Behav. 1987, 27, 253-256.
5. Porsolt, R. D.; Lenègre, A.; Avril, I.; Lancrenon, S.; Stéru, L.; Doumont, G. Psychopharmacological profile on the new cognition enhancing agent exifone in the mouse. Arzneim. Forsch. Drug Res. 1987, 37, 388-393.
6. Porsolt, R. D.; Lenègre, A.; Avril, I.; Doumont, G. Antagonism by exifone, a new cognitive enhancing agent, of the amnesias induced by four benzodiazepines in mice. Psychopharmacology 1988, 95, 291-297.
7. Allain, H.; Denmat, J.; Bentue-Ferrer, D.; Milon, D.; Pignol, P.; Reymann, J. M.; Pape, D.; Sabouraud, O.; Van den Driessche, J. Randomized, double-blind trial of exifone versus cognitive problems in Parkinson's disease. Fundam. Clin. Pharmacol. 1988, 2, 1-12.
8. Bentue-Ferrer, D.; Philouze, V.; Pape, D.; Reymann, J. M.; Allain, H.; Van den Driessche, J. Comparative evaluation of scavenger properties of exifone, piracetam and vinburnine. Fundam. Clin. Pharmacol. 1989, 3, 323-328.
9. Collins, M. A. A possible neurochemical mechanism for brain and nerve damage associated with chronic alcoholism. Trends Pharmacol. Sci. 1982, 3, 373-375.
10. Dahlin, D. C.; Nelson, S. D. Synthesis, decomposition kinetics, and preliminary toxicological studies of pure N-acetyl-p-benzoquinone imine, a proposed toxic metabolite of acetaminophen. J. Med. Chem. 1982, 25, 885-886.
11. Smilkstein, M. J.; Knapp, G. L.; Kulig, K. W.; Rumack, B. H. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. New Engl. J. Med. 1988, 319, 1557-1562.
12. Zhang, F.; Dryhurst, G. Oxidation chemistry of the endogenous central nervous system alkaloid salsolinol. Bioorg. Chem. 1991, 19, 384-397.
13. Zhang, F.; Dryhurst, G. Synthesis and oxidation chemistry of 8-S-cysteinyl conjugates of salsolinol. Bioorg. Chem. 1993, 21, 221-237.
14. Shen; X. M.; Dryhurst, G. Further insights into the oxidation chemistry of norepinephrine and epinephrine in the presence of cysteine. Bioorg. Chem. 1997, 25, 130-153.
15. Fleury, M.-B.; Maurette, J.-M.; Largeron, M. Preparation of acylbenzoxazine for use in the treatment of free radical based cerebral pathology. PCT Int. Appl. WO 95 18114/1995 (Chem. Abstr. 1995, 123, 340 160x).
16. Largeron, M.; Dupuy, H.; Fleury, M.-B. Novel 1,4-benzoxazine derivatives of pharmacological interest. Electrochemical and chemical syntheses. Tetrahedron 1995, 51, 4953-4968.
17. Chacun-Lefevre, L.; Buon, C.; Bouyssou, P.; Coudert, G. Synthesis of 3-substituted-4H-1,4-benzoxazines. Tetrahedron Lett. 1998, 39, 5763-5764.
18. Matsumoto, Y.; Tsuzuki, R.; Matsuhisa, A.; Takayama, K.; Yoden, T.; Uchida, W.; Asano, M.; Fujita, S.; Yanagisawa, I.; Fujikura, T. Novel potassium channel activators: synthesis and struture activity relationship studies of 3,4-dihydro-2H-1,4-benzoxazine derivatives. Chem. Pharm. Bull 1996, 44, 103-114.
19. 3) receptor antagonists. Chem. Pharm. Bull. 1996, 44, 756-764.
20. Hays, S. J.; Caprathe, B. W.; Gilmore, J. L.; Amin, N.; Emmerling, M. R.; Michael, W.; Nadimpalli, R.; Nath, R.; Raser, K. J.; Stafford, D.; Watson, D.; Wang, K.; Jaen, J. C. 2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease. J. Med. Chem. 1998, 41, 1060-1067.
21. Bourlot, A.-S.; Sanchez, I.; Dureng, G.; Guillaumet, G.; Massingham, R.; Monteil, A.; Winslow, E.; Dorlos Pujol, M.; Mérou, J.-Y. New substituted 1,4-benzoxazine derivatives with potential intracellular calcium activity. J. Med. Chem. 1998, 41, 3142-3158.
22. Largeron, M.; Fleury, M.-B. A convenient two-step one-pot electrochemical synthesis of novel 8-amino-1,4-benzoxazine derivatives possessing anti-stress oxidative properties. Tetrahedron Lett. 1998, 39, 8999-9002.
23. Thor, H.; Smith, M. T.; Hartzell, P.; Bellomo, G.; Jewell, S. A.; Orrenius, S. The metabolism of Menadione (2-methyl-1,4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells. J. Biol. Chem. 1982, 257, 12419-12425.
24. Murphy, T. H.; Miyamoto, M.; Sastre, A.; Schnaar, R. L.; Coyle, J. T. Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron 1989, 2, 1547-1558.
25. Ratan, R. R.; Murphy, T. H.; Baraban, J. M. Oxidative stress induces apoptosis in embryonic cortical neurons. J. Neurosci. 1994, 62, 376-379.
26. Largeron, M.; Langevin-Bermond, D.; Fleury, M.-B. Determination of the sequential order of acidity in a polyhydroxylated benzophenone series. Consequence on the oxidation reaction in relation to hepatotoxicity. J. Chem. Soc., Perkin Trans. 2 1996, 893-899.
27. Morimoto, B. H.; Koshland, D. E. Induction and expression of long- and short-term neurosecretory potentiation in a neuronal cell line. Neuron 1989, 5, 875-880.
28. Behl, C.; Trapp, T.; Skutella, T.; Holsboer, F. Protection against oxidative stress-induced neuronal cell death. A novel role for RU 486. Eur. J. Neurosci, 1997, 9, 912-920.
29. Mosmann, T. Rapid calorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Immunol. Methods 1983, 65, 55-63.