Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 10, 2007, Pages 2834-2837

  Roggen, Heidi ^a   Kehler, Jan ^b   Stensbøl, Tine Bryan ^b   Hansen, Tore ^a  

^a UNIVERSITY OF OSLO   (Norway)

^b H LUNDBECK A S   (Denmark)

Author keywords

Dopamine; Milnacipran analogs; Norepinephrine; Serotonin; Synthesis; Uptake inhibition

Indexed keywords

CYCLOPROPANE DERIVATIVE; DOPAMINE TRANSPORTER; MILNACIPRAN DERIVATIVE; NORADRENALIN TRANSPORTER; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; DRUG INHIBITION; ENANTIOMER; PROTEIN SYNTHESIS;

CYCLOPROPANES; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DRUG DESIGN; MEMBRANE TRANSPORT PROTEINS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; NOREPINEPHRINE PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 34247344957     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.02.054     Document Type: Article

References (28)

1. Amara S.G. Neurotransmitter Transporters (1998), Academic Press, San Diego, CA
2. Hahn M.K., and Blakely R.D. Pharmacogenom. J. 2 (2002) 217
3. Heinz A., Mann K., Weinberger D.R., and Goldman D. Alcohol Clin. Exp. Res. 25 (2001) 487
4. Klimek V., Stockmeier C., Overholser J., Meltzer H.Y., Kalka S., Dilley G., and Ordway G.A. J. Neurosci. 17 (1997) 8451
5. Robertson D., Flattem N., Tellioglu T., Carson R., Garland E., Shannon J.R., Jordan J., Jacob G., Blakely R.D., and Biaggioni I. Ann. N. Y. Acad. Sci. 940 (2001) 527
6. Miller G.M., De La Garza II R., Novak M.A., and Madras B.K. Mol. Psychiatry 6 (2001) 50
7. Ozaki N., Goldman D., Kaye W.H., Plotnicov K., Greenberg B.D., Lappalainen J., Rudnick G., and Murphy D.L. Mol. Psychiatry 8 (2003) 933
8. Kuhar M.J., Ritz M.C., and Boja J.W. Trends Neurosci. 14 (1991) 29
9. Ritz M.C., Lamb R.J., Goldberg S.R., and Kuhar M.J. Science 237 (1987) 1219
10. Millan M.J. Eur. J. Pharmacol. 500 1-3 (2004) 37
11. Humble M. Acta Psychiatrica Scandin. 101 (2000) 28
12. Wong D.T., Bymaster F.P., and Engleman E.A. Life Sci. 57 (1995) 411
13. Beasley Jr. C.M., Holman S.L., and Potvin J.H. Ann. Clin. Psychiatry 5 (1993) 199
14. Cookson J. Br. J. Psychiatry Suppl. 20 (1993) 20-24
15. Stahl S.M., Grady M.M., Moret C., and Briley M. CNS Spectr. 10 (2005) 732
16. The authors that reported the initial discovery of milnacipran did not describe transporter activity of milnacipran and its derivatives. See:. Bonnaud B., Cousse H., Mouzin G., Briley M., Stenger A., Fauran F., and Couzinier J.P. J. Med. Chem. 30 (1987) 318
17. Kazuta Y., Tsujita R., Yamashita K., Uchino S., Kohsaka S., Matsuda A., and Shuto S. Bioorg. Med. Chem. 10 (2002) 3829
18. Shuto S., Takada H., Mochizuki D., Tsujita R., Hase Y., Ono S., Shibuya N., and Matsuda A. J. Med. Chem. 38 (1995) 2964
19. Shuto S., Ono S., Hase Y., Ueno Y., Noguchi T., Yoshii K., and Matsuda A. J. Med. Chem. 39 (1996) 4844
20. Shuto S., Ono S., Imoto H., Yoshii K., and Matsuda A. J. Med. Chem. 41 (1998) 3507
21. Shuto S., Ono S., Hase Y., Kamiyama N., Takada H., Yamasihita K., and Matsuda A. J. Org. Chem. 61 (1996) 915
22. Kazuta Y., Tsujita R., Ogawa K., Hokonohara T., Yamashita K., Morino K., Matsuda A., and Shuto S. Bioorg. Med. Chem. 10 (2002) 1777
23. 2 for 10 min at 37 °C and pH is adjusted to 7.4. The incubation is started by adding tissue to a final assay volume of 0.2 mL. After 15-min incubation with radioligand at 37 °C, samples are filtered directly on Unifilter GF/C glass fiber filters (soaked for 1 h in 0.1% polyethylenimine) under vacuum and immediately washed with 3× 0.2 ml assay buffer. Non-specific uptake is determined using citalopram (10 μM final concentration). Citalopram is included as reference in all experiments as dose-response curve.
24. Vaishnavi S.N., Nemeroff C.B., Plott S.J., Rao S.G., Kranzler J., and Owens M.J. Biol. Psychiatry 55 (2004) 320
25. Axford L., Boot J.R., Hotten T.M., Keenan M., Martin F.M., Milutinovic S., Moore N.A., O'Neill M.F., Pullar I.A., Tupper D.F., Van Belle K.R., and Vivien V. Bioorg. Med. Chem. Lett. 13 (2003) 3277
26. Masand P.S., Anand V.S., and Tanquary J.F. Depress Anxiety 7 (1998) 89
27. Nelson J.C. J. Clin. Psychiatry 59 Suppl. 5 (1998) 65-68 discussion 69
28. Ashton A.K., and Rosen R.C. J. Clin. Psychiatry 59 (1998) 112