Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3- piperidinylpropan-2-ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 4

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 10, 2004, Pages 2653-2656

  Rocco, Vincent P ^a   Spinazze, Patrick G ^a   Kohn, Todd J ^a   Honigschmidt, Nicholas A ^a   Nelson, David L ^a   Bradley Wainscott, D ^a   Ahmad, Laura J ^a   Shaw, Janice ^a   Threlkeld, Penny G ^a   Wong, David T ^a   Takeuchi, Kumiko ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDEPRESSANT AGENT; PIPERIDINE DERIVATIVE; SEROTONIN 1 ANTAGONIST; SEROTONIN UPTAKE INHIBITOR;

ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; STEREOCHEMISTRY;

ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; PROPANOLS; PROTEIN BINDING; RECEPTOR, SEROTONIN, 5-HT1A; SEROTONIN UPTAKE INHIBITORS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 11144357669     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.02.088     Document Type: Article

References (14)

1. Annanth J. Psychother. Psychosom. 67:1998;61.
2. Evrard D.A., Harrison B.L. Annu. Rep. Med. Chem. 34:1999;1.
3. Rutter J.J., Gundlah C., Auerbach S.B. Synapse. 20:1995;225.
4. Tome' M.B., Isaac M.T., Harte R., Holland C. Int. Clin. Psychopharmacol. 12:1997;81.
5. Zanardi R., Artigas F., Franchini L.et al. J. Clin. Psychopharmacol. 17:1997;446.
6. Takeuchi K., Kohn T.J., Honigschmidt N.A., Rocco V.P., Spinazze P.G., Koch D.J., Nelson D.L., Wainscott D.B., Ahmad L.J., Shaw J., Threlkeld P.G., Wong D.T. Bioorg. Med. Chem. Lett. 13:2003;1903.
7. Takeuchi K., Kohn T.J., Honigschmidt N.A., Rocco V.P., Spinazze P.G., Koch D.J., Atkinson S.T., Hertel L.W., Nelson D.L., Wainscott D.B., Ahmad L.J., Shaw J., Threlkeld P.G., Wong D.T. Bioorg. Med. Chem. Lett. 13:2003;2393.
8. Takeuchi K., Kohn T.J., Honigschmidt N.A., Rocco V.P., Spinazze P.G., Atkinson S.T., Hertel L.W., Nelson D.L., Wainscott D.B., Ahmad L.J., Shaw J., Threlkeld P.G., Wong D.T. Bioorg. Med. Chem. Lett. 13:2003;3939.
9. 6,7 Compounds 2, 4, and 6 were prepared from 3-bromobenzo[b]thiophene or appropriately substituted 2-bromonaphthalenes by the same protocol after the metal-halogen exchange.
10. 1A receptor with standard assay techniques as previously described: Weinshank R.L., Zgombick J.M., Macchi M.J., Brancheck T.A., Hartig P.R. Proc. Natl. Acad. Sci. U.S.A. 89:1992;3630.
11. Radioligand assays were performed in triplicates, using rat frontal cortex membranes: Wong D.T., Threlkeld P.G., Robertson D.W. Neuropsychopharmacology. 5:1991;43.
12. The method was based on an assay previously described but adapted to a scintillation proximity assay (SPA) format. See Rasmussen K., Calligaro D.O., Czachura J.F., Dreshfield-Ahmad L.J., Evans D.C., Hemrick-Luecke S.K., Kallman M.J., Kendrick W.T., Leander J.D., Nelson D.L., Overshiner C.D., Wainscott D.B., Wolff M.C., Wong D.T., Brancheck T.A., Zgombick J.M., Xu Y.-C. J. Pharmacol. Exp. Ther. 294:2000;688.
13. Plé P.A., Marnett L.J. J. Heterocycl. Chem. 25:1988;1271.
14. max 4.1% in GTPγS functional assay).