Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position

Fanxing Zeng; Nachwa Jarkas; Michael J. Owens; Clinton D. Kilts; Charles B. Nemeroff; Mark M. Goodman

doi:10.1016/j.bmcl.2006.05.098

Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position

Fanxing Zeng, Nachwa Jarkas, Michael J. Owens, Clinton D. Kilts, Charles B. Nemeroff, Mark M. Goodman

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

A series of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position was synthesized, and their binding affinities were determined in cells transfected to express human norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT) via competition binding assays. All compounds studied in this series exhibit a moderate to high potency at all three transporters with SERT or DAT selectivity. 3β-(4′-iodo)phenyltropane bearing methylene on the bridge to the 2β-position (24) presents a particularly attractive pharmacological profile, with very high SERT affinity (K_i = 0.09 nM) and selectivity versus NET (65-fold) and DAT (94-fold).

Original language	English (US)
Pages (from-to)	4661-4663
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2006.05.098
State	Published - Sep 1 2006
Externally published	Yes

Keywords

Carbon-11
NET
PET
SERT
Tropane

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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Zeng, F., Jarkas, N., Owens, M. J., Kilts, C. D., Nemeroff, C. B., & Goodman, M. M. (2006). Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position. Bioorganic and Medicinal Chemistry Letters, 16(17), 4661-4663. https://doi.org/10.1016/j.bmcl.2006.05.098

Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position. / Zeng, Fanxing; Jarkas, Nachwa; Owens, Michael J.; Kilts, Clinton D.; Nemeroff, Charles B.; Goodman, Mark M.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 17, 01.09.2006, p. 4661-4663.

Research output: Contribution to journal › Article › peer-review

Zeng, F, Jarkas, N, Owens, MJ, Kilts, CD, Nemeroff, CB & Goodman, MM 2006, 'Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 17, pp. 4661-4663. https://doi.org/10.1016/j.bmcl.2006.05.098

Zeng F, Jarkas N, Owens MJ, Kilts CD, Nemeroff CB, Goodman MM. Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position. Bioorganic and Medicinal Chemistry Letters. 2006 Sep 1;16(17):4661-4663. https://doi.org/10.1016/j.bmcl.2006.05.098

Zeng, Fanxing ; Jarkas, Nachwa ; Owens, Michael J. ; Kilts, Clinton D. ; Nemeroff, Charles B. ; Goodman, Mark M. / Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 17. pp. 4661-4663.

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abstract = "A series of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position was synthesized, and their binding affinities were determined in cells transfected to express human norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT) via competition binding assays. All compounds studied in this series exhibit a moderate to high potency at all three transporters with SERT or DAT selectivity. 3β-(4′-iodo)phenyltropane bearing methylene on the bridge to the 2β-position (24) presents a particularly attractive pharmacological profile, with very high SERT affinity (Ki = 0.09 nM) and selectivity versus NET (65-fold) and DAT (94-fold).",

keywords = "Carbon-11, NET, PET, SERT, Tropane",

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AU - Jarkas, Nachwa

AU - Owens, Michael J.

AU - Kilts, Clinton D.

AU - Nemeroff, Charles B.

AU - Goodman, Mark M.

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Synthesis and monoamine transporter affinity of front bridged tricyclic 3β-(4′-halo or 4′-methyl)phenyltropanes bearing methylene or carbomethoxymethylene on the bridge to the 2β-position

Abstract

Keywords

ASJC Scopus subject areas

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