2,3-Disubstituted 6-azabicyclo[3.2.1]octanes as novel dopamine transporter inhibitors

Bioorganic and Medicinal Chemistry

Volumn 12, Issue 6, 2004, Pages 1383-1391

  Quirante, Josefina ^a   Vila, Xavier ^a   Bonjoch, Josep ^a   Kozikowski, Alan P ^b   Johnson, Kenneth M ^c  

^a UNIVERSITY OF BARCELONA   (Spain)

^b GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^c University of Texas Medical Branch School of Medicine   (United States)

Author keywords

6 Azabicyclo 3.2.1 octane; Cocaine; Dopamine uptake; Normorphan analogues

Indexed keywords

2ALPHA CARBOMETHOXY 6 METHYL 3BETA (4 CHLOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 3BETA (4 TOLYL) 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 3BETA (FLUOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 3BETA PHENYL 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 7 OXO 3BETA (4 CHLOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 7 OXO 3BETA (4 FLUOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 7 OXO 3BETA (4 TOLYL) 6 AZABICYCLO[3.2.1]OCTANE; 2ALPHA CARBOMETHOXY 6 METHYL 7 OXO 3BETA PHENYL 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 3BETA (4 CHLOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 3BETA (4 FLUOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 3BETA (4 TOLYL) 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 3BETA PHENYL 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 7 OXO 3BETA (4 CHLOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 7 OXO 3BETA (4 FLUOROPHENYL) 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 7 OXO 3BETA (4 TOLYL) 6 AZABICYCLO[3.2.1]OCTANE; 2BETA CARBOMETHOXY 6 METHYL 7 OXO 3BETA PHENYL 6 AZABICYCLO[3.2.1]OCTANE; COCAINE; DOPAMINE; DOPAMINE TRANSPORTER; DOPAMINE UPTAKE INHIBITOR; OCTANE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; MALE; NONHUMAN; RAT; SUBSTITUTION REACTION;

ANIMALS; AZA COMPOUNDS; BICYCLO COMPOUNDS, HETEROCYCLIC; BIOLOGICAL TRANSPORT; COCAINE; DOPAMINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DOPAMINE UPTAKE INHIBITORS; LIGANDS; MALE; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; MOLECULAR STRUCTURE; NERVE TISSUE PROTEINS; OCTANES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; SYNAPTOSOMES;

EID: 1542331633     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2004.01.019     Document Type: Article

References (54)

1. Lounasmaa, M. In The Alkaloids; Brossi, A., Ed.; Academic Press Inc.: New York, 1988; Vol. 33, pp 1-83.
2. Ritz M.C., Lamb R.J., Goldberg S.R., Kuhar M.J. Science. 237:1987;1219.
3. Kuhar M.J., Ritz M.C., Boja J.W. Trends Neurosci. 14:1991;299.
4. Koob G.F., Bloom F.E. Science. 242:1988;715.
5. Kuhar M.J., Pilotte N.S. Trends. Pharmacol. Sci. 17:1996;260.
6. Lin Z., Wang W., Kopajtic T., Revay R., Uhl G. Mol. Pharmacol. 56:1999;434.
7. Smith M.P., Hoepping A., Johnson K.M., Trzcinska M., Kozikowski A.P. Drug Discov. Today. 4:1999;332.
8. Carroll F.I., Howell L.L., Kuhard M.J. J. Med. Chem. 42:1999;2721.
9. Carroll F.I., Lewin A.H., Boja J.W., Kuhar M.J. J. Med. Chem. 35:1992;969.
10. Meltzer P.C., Blundell P., Madras B.K. Med. Chem. Res. 8:1998;12.
11. Singh S. Chem. Rev. 100:2000;925.
12. Tamiz A., Zhang J., Flippen-Anderson J., Zhang M., Johnson K.M., Deschaux O., Tella S., Kozikowski A.P. J. Med. Chem. 43:2000;1215.
13. Hoepping A., Johnson K.M., George C., Flippen-Anderson J., Kozikowski A.P. J. Med. Chem. 43:2000;2064.
14. Zhao L., Johnson K.M., Zhang M., Flippen-Anderson J., Kozikowski A.P. J. Med. Chem. 43:2000;3283.
15. For previous synthetic work, concerning the preparation of this azabicyclic framework by intramolecular radical cyclization through 1-aminomethyl radical intermediates, see: Quirante J., Escolano C., Bonjoch J. Synlett. 1997;179.
16. For natural products containing the 6-azabicyclo[3.2.1]octane structure, see: Quirante J., Vila X., Escolano C., Bonjoch J. J. Org. Chem. 67:2002;2323. and ref. 1-6 cited therein.
17. For recent synthesis of 6-azabicyclo[3.2.1]octanes, see: (a) Pitner J.B., Abraham P., Joo Y.J., Triggle D.J., Carroll F.I. J. Chem. Soc., Perkin Trans. 1. 1991;1375.
18. Callis D.J., Thomas N.F., Pearson D.P.J., Potter B.V.L. J. Org. Chem. 61:1996;4634.
19. Rigby J.H., Pigge F.C. Tetrahedron Lett. 37:1996;2201.
20. Rigby J.H., Pigge F.C. Synlett. 1996;631.
21. Davies H.M.L., Cao G. Tetrahedron Lett. 39:1998;5943.
22. Lin X., Stien D., Weinreb S.M. Tetrahedron Lett. 41:2000;2333.
23. Han G., LaPorte M.G., Folmer J.J., Werner K.M., Weinreb S.T. J. Org. Chem. 65:2000;6294.
24. Roberson C.W., Woerpel K.A. Org. Lett. 2:2000;621.
25. (i) see also refs. 6 and 7.
26. Carroll F.I., Abraham P., Parham K., Griffith R.C., Ahmad A., Richard M.M., Padilla F.N., Witkin J.M., Chiang P.K. J. Med. Chem. 30:1987;805.
27. Carroll F.I., Abraham P., Mascarella S.W., Singh P., Moreland C.G., Sankar S.S., Kwon Y.W., Triggle D.J. J. Med. Chem. 34:1991;1436.
28. Abraham P., Pitner J.B., Mascarella S.W., Carroll F. J. Med. Chem. 34:1991;3164.
29. Abraham P., Pitner J.B., Lewin A.H., Boja J.W., Kuhar M.J., Carroll F.I. J. Med. Chem. 35:1992;141.
30. Clarke R.L., Daum S.J., Gambino A.J., Aceto M.D., Pearl J., Lewitt M., Cumiskey W.R., Bogado E.F. J. Med. Chem. 16:1973;1260.
31. Carroll F.I., Gao Y., Rahman M.A., Abraham P., Parham K., Lewin A.H., Boja J.W., Kuhar M.J. J. Med. Chem. 34:1991;2719.
32. Carroll F.I., Kotian P., Deghani A., Gray J.L., Kuzembo M.A., Parham K.A., Abraham P., Lewin A.H., Boja J.W., Kuhar M. J. Med. Chem. 38:1995;379.
33. Kozikowski A.P., Eddine Saiah M.K., Johnson K.M., Bergmann J.S.J. Med. Chem. 38:1995;3086.
34. Kozikowski A.P., Araldi G.L., Prakash K.R.C., Zhang M., Johnson K.M. J. Med. Chem. 41:1998;4973.
35. Zhao L., Kozikowski A.P. Tetrahedron Letters. 40:1999;4961.
36. Blough B.E., Holmquist C.R., Abraham P., Kuhar M.J., Carroll F.I. Bioorg. Med. Chem. Lett. 10:2000;2445.
37. Davies H.M.L., Ren P., Kong N., Sexton T., Childers S.R. Bioorg. Med. Chem. 11:2001;487.
38. Meltzer P.C., Wang B., Chen Z., Blundell P., Jayaraman M., Gonzalez M.D., George C., Madras B. J. Med. Chem. 44:2001;2619. For a rewiew see also ref. 5c.
39. Tomisawa H., Hongo H., Hatano T., Nakano H., Fujita R. Chem. Pharm. Bull. 35:1987;530.
40. Examples inter alia using TFA at -78 °C: Carroll F.I., Gao I., Rahman M.A., Abraham P., Parham K., Lewin A.H., Boja J.W., Kuhar M.J. J. Med. Chem. 34:1991;2719.
41. Xu L., Trudell M.L. J. Heterocyclic Chem. 33:1996;2037.
42. (c) ref. 11d.
43. Examples inter alia using ethereal HCl at low temperatures (-20 °C, -78 °C): (a) Meltzer P.C., Liang A.Y., Brownell A.L., Elmaleh D.R., Madras B.K. J. Med. Chem. 36:1993;855.
44. Davies H.M.L., Saikali E., Huby N.J.S., Gilliatt V.J., Matasi J.J., Sexton T., Childers S.R. J. Med. Chem. 37:1994;1262.
45. Davies H.M.L., Gilliat V., Kuhn L.A., Saikali E., Ren P., Hammond P.S., Sexton T., Childers S.R. J. Med. Chem. 44:2001;1509.
46. (d) ref 11h.
47. For recent studies about the influence of the bridging heteroatom β, to the carbonyl group in the enolate protonation from the endo face, see: Davies H.M., Hodges L.M., Gregg T.M. J. Org. Chem. 66:2001;7898.
48. For a review on kinetic protonation of enol, enolates and related intermediates see: Zimmerman H.E. Acc. Chem. Res. 20:1987;263.
49. Collins C.J., Lanz M., Singaram B. Tetrahedron Lett. 40:1999;3673.
50. Wang S., Sakamuri S., Enyedy I.J., Kozikowski A.P., Deschaux O., Bandyopadhyay B.C., Tella S.R., Zaman W.A., Johnson K.M. J. Med. Chem. 43:2000;351.
51. Kozikowski A.P., Eddine Saiah M.K., Bergmann J.S., Johnson K.M. J. Med. Chem. 37:1994;3440.
52. Meltzer P.C., Liang A.Y., Blundell P., Gonzalez M.D., Chen Z., George C., Madras B.K. J. Med. Chem. 40:1997;2661.
53. Carroll F.I., Gao I., Rahman M.A., Abraham P., Parham K., Lewin A.H., Boja J.W., Kuhar M.J. J. Med. Chem. 34:1991;2719.
54. Carroll F.I., Mascarella S.W., Kuzemko M.A., Gao Y., Abraham P., Lewin A.H., Boja J.W., Kuhar M.J. J. Med. Chem. 37:1994;2865.