Synthesis of 4-(aminoalkyl) substituted 1,3-dioxanes as potent NMDA and σ receptor antagonists

European Journal of Medicinal Chemistry

Volumn 46, Issue 6, 2011, Pages 2157-2169

  Utech, Tina ^a   Köhler, Jens ^a   Wünsch, Bernhard ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

Receptor affinity; 1,3 Dioxanes; Dexoxadrol homologues; NMDA receptor antagonists; PCP binding site; Structure affinity relationships

Indexed keywords

2 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL) N METHYLETHAN 1 AMINE; 2 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 AMINE; 2 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 OL; 2 (2 PHENYL 1,3 DIOXAN 4 YL) ETHAN 1 AMINE; 2 (2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 OL; 2 (2,2 DIPHENYL 1,3 DIOXAN 4 YL) N METHYLETHAN 1 AMINE; 2 (2,2 DIPHENYL 1,3 DIOXAN 4 YL) N,N DIMETHYLETHAN 1 AMINE; 2 (2,2 DIPHENYL 1,3 DIOXAN 4 YL)ETHAN 1 OL; 2 [SPIRO(ADAMANTAN 2,2' [1,3]DIOXAN) 4' YL]ETHAN 1 AMINE; 2 [SPIRO(ADAMANTAN 2,2' [1,3]DIOXAN) 4' YL]ETHANOL; 3 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL)PROPANENITRILE; 3 (2 PHENYL 1,3 DIOXAN 4 YL)PROPAN 1 AMINE; 4 (2 AZIDOETHYL) 2 PHENYL 1,3 DIOXANE; 4' (2 AZIDOETHYL)SPIRO(ADAMANTAN 2,2' [1,3]DIOXANE); [2 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL)] N,N DIMETHYLETHAN 1 AMINE; [2 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL)ETHYL] 4 TOLUENESULFONATE; [2 (2 PHENYL 1,3 DIOXAN 4 YL)ETHYL] 4 TOLUENESULFONATE; [2 (2,2 DIPHENYL 1,3 DIOXAN 4 YL)ETHYL] 4 TOLUENESULFONATE; [2 [SPIRO(ADAMANTAN 2,2' [1,3]DIOXAN) 4' YL]ETHYL] 4 TOLUENESULFONATE; ADAMANTAN 2 ONE DIMETHYL ACETAL; ANALGESIC AGENT; DEXOXADROL; ETOXADROL; N BENZYL 2 (2 ETHYL 2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 AMINE; N BENZYL 2 (2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 AMINE; N BENZYL 2 (2,2 DIPHENYL 1,3 DIOXAN 4 YL)ETHAN 1 AMINE; N METHYL 2 (2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 AMINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; N,N DIMETHYL 2 (2 PHENYL 1,3 DIOXAN 4 YL)ETHAN 1 AMINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG STRUCTURE; MOUSE; NONHUMAN;

ANIMALS; BRAIN; DIOXANES; MOLECULAR STRUCTURE; RECEPTORS, N-METHYL-D-ASPARTATE; RECEPTORS, SIGMA; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SWINE;

EID: 79955580441     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.02.070     Document Type: Article

References (49)

1. J.N.C. Kew, J.A. Kemp, Psychopharmacology 179 (2005) 4-29.
2. S. Maren, M. Baudry, Neurobiol. Learn. Mem. 63 (1995) 1-18.
3. H. Brauner-Osborne, J. Egebjerg, E.O. Nielsen, U. Madsen, P. Krogsgaard- Larsen, J. Med. Chem. 43 (2000) 2609-2645.
4. N. Rebola, B.N. Srikumar, C. Mulle, J. Physiol. 588 (2010) 93-99.
5. M.F. Beal, FASEB J. 6 (1992) 3338-3344.
6. C. Villmann, C.-M. Becker, Neuroscience 13 (2007) 594-615.
7. S.A. Lipton, Nature Rev. Drug Disc. 5 (2006) 160-170.
8. E.H.F. Wong, J.A. Kemp, Annu. Rev. Phrmacol. Toxicol. 31 (1991) 401-425.
9. H. Stark, U. Reichert, S. Graßmann, Pharm. U.Z. 20 (2000) 226-236.
10. W.R. Hardie, J. Hidalgo, J.F. Halverstadt, R.E. Allen, J. Med. Chem. 9 (1966) 127-136.
11. J. Hidalgo, C.R. Thompson, Arch. Int. Pharmacodyn. 153 (1965) 105-125.
12. A.H. Tang, J.D. Kirch, Anesth. Analg. 52 (1973) 577-583.
13. L. Lasagna, J.W. Pearson, Proc. Soc. Exp. Biol. Med. 118 (1965) 352-354.
14. E.L. Frederickson, D.E. Longnecker, G.W. Allen, Anesth. Analg. 55 (1976) 335-339.
15. L.G. Mendelson, G.A. Kerchner, V. Katra, D.H. Zimmermann, J.D. Leander, Biochem. Pharmacol. 33 (1984) 3529-3535.
16. R.Y. Hampton, F. Medzihdradsky, J.H. Woods, P.J. Dahlström, Life Sci. 30 (1982) 2147-2154.
17. A. Thurkauf, M.V. Mattson, S. Richardson, S. Mirsadeghi, P.L. Ornstein, E.A. Harrison Jr., K.C. Rice, A.E. Jacobson, J.A. Monn, J. Med. Chem. 35 (1992) 1323-1329.
18. M. Aepkers, B. Wünsch, Bioorg. Med. Chem. 13 (2005) 6836-6849.
19. M. Sax, B. Wünsch, Curr. Top. Med. Chem. 6 (2006) 723-732.
20. E.F. Domino, J.-M. Kamenka (Eds.), Sigma and Phencyclidine - Like Compounds as Molecular Probes in Biology (1988) Ann Arbor, MI 48106, pp. 19-25, 35-45, 47-54.
21. M. Aepkers, B. Wünsch, Arch. Pharm. Pharm. Med. Chem. 337 (2004) 67-75.
22. A. Thurkauf, P.C. Zenk, R.L. Balster, E.L. May, C. George, F.I. Carroll, S.W. Mascarella, K.C. Rice, A.E. Jacobson, M.V. Mattson, J. Med. Chem. 31 (1988) 2257-2263.
23. M. Sax, K. Ebert, D. Schepmann, B. Wibbeling, B. Wünsch, Bioorg. Med. Chem. 14 (2006) 5955-5962.
24. M. Sax, R. Fröhlich, D. Schepmann, B. Wünsch, Eur. J. Org. Chem. (2008) 6015-6028.
25. A. Banerjee, R. Fröhlich, D. Schepmann, B. Wünsch, Med. Chem. Commun. 1 (2010) 87-102.
26. A. Banerjee, D. Schepmann, B. Wünsch, Bioorg. Med. Chem. 18 (2010) 4095-4102.
27. M. Viscontini, C. Ebnöther, Helv. Chim. Acta 34 (1951) 116-118.
28. W.F. Bailey, H. Connon, E.L. Eliel, K.B. Wiberg, J. Am. Chem. Soc. 100 (1978) 2202-2209.
29. F.W. Nader, Tetrahedron Lett. 16 (1975) 1591-1594.
30. E. Langer, H. Lehner, Monatsh. Chem. 107 (1976) 1-17.
31. P. Krasutsky, J. Org. Chem. 65 (2000) 3926-3933.
32. M. Aepkers, B. Wünsch, Synthesis 7 (2004) 1033-1036.
33. B. Wünsch, H. Diekmann, Liebigs Ann. (1996) 69-76 references cited therein.
34. J. Mancuso, D. Swern, Synthesis (1981) 165-185.
35. R.M. McKernan, S. Castro, J.A. Poat, E.H.F. Wong, J. Neurochem. 52 (1989) 777-785.
36. G. Höfner, K.T. Wanner, J. Rec. Sign. Transd. Res. 16 (1996) 297-313.
37. U. Wirt, D. Schepmann, B. Wünsch, Eur. J. Org. Chem. (2007) 462-475.
38. F.I. Carroll, P. Abraham, K. Parham, X. Bai, X. Zhang, G.A. Brine, S.W. Mascarella, B.R. Martin, E.L. May, C. Sauss, et al., J. Med. Chem. 35 (1992) 2812-2818.
39. E.L. May, M.D. Aceto, E.R. Bowman, C. Bentley, B.R. Martin, L.S. Harris, F. Medzihradsky, M.V. Mattson, A. Jacobson, Eur. J. Med. Chem. 37 (1994) 3408-3418.
40. C. Kaiser, M.J. Pontecorvo, R.E. Mewshaw, Neurotransmissions 7 (1991) 1-5.
41. L. Brasili, Pharm. Acta Helv. 74 (2000) 201-203.
42. W.D. Bowen, Pharm. Acta Helv. 74 (2000) 211-218.
43. C.A. Maier, B. Wünsch, J. Med. Chem. 45 (2002) 438-448.
44. C.A. Maier, B. Wünsch, J. Med. Chem. 45 (2002) 4923-4930.
45. T. Utech, J. Köhler, B. Wünsch, Arch. Pharm. Chem. Life Sci., in press.
46. J.L. Diaz, D. Zamanillo, J. Corbera, J.M. Baeyens, R. Maldonado, M.A. Perica, J.M. Vela, A. Torrens, Centr. Nerv. Syst. Agents Med. Chem. 9 (2009) 172-183.
47. H.D. Gilchrist, B.L. Allard, D.A. Simone, Pain 67 (1996) 179-188.
48. Y. Cheng, W.H. Prusoff, Biochem. Pharmacol. 22 (1973) 3099-3108.
49. M.M. Bradford, Anal. Biochem. 72 (1976) 248-254.