Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents

Fanxing Zeng, Jeffrey S. Stehouwer, Nachwa Jarkas, Ronald J. Voll, Larry Williams, Vernon M. Camp, John R. Votaw, Michael J. Owens, Clinton D. Kilts, Charles B. Nemeroff, Mark M. Goodman

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

A series of 2β,3α-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [11C]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [11C]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET.

Original languageEnglish (US)
Pages (from-to)3044-3047
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number11
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

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Keywords

  • Carbon-11
  • Imaging
  • MicroPET
  • NET
  • PET

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Zeng, F., Stehouwer, J. S., Jarkas, N., Voll, R. J., Williams, L., Camp, V. M., Votaw, J. R., Owens, M. J., Kilts, C. D., Nemeroff, C. B., & Goodman, M. M. (2007). Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents. Bioorganic and Medicinal Chemistry Letters, 17(11), 3044-3047. https://doi.org/10.1016/j.bmcl.2007.03.056