Development of Polyfluorophenyltropanes: Potential Probes for 19F Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) Assessments of the Dopamine Transporter

Ao Zhang; Nora S. Kula; Kehong Zhang; Ross J. Baldessarini; Marc J. Kaufman; Perry F. Renshaw; John L. Neumeyer

doi:10.2174/1570180054038332

ISSN: 1570-1808
E-ISSN: 1875-628X

Development of Polyfluorophenyltropanes: Potential Probes for 19F Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) Assessments of the Dopamine Transporter
Authors: Ao Zhang¹, Nora S. Kula², Kehong Zhang³, Ross J. Baldessarini⁴, Marc J. Kaufman⁵, Perry F. Renshaw⁶ and John L. Neumeyer⁷
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¹ Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA. ² Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA. ³ Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA. ⁴ Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA. ⁵ Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA. ⁶ Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA. ⁷ Medicinal Chemistry Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA.
Source: Letters in Drug Design & Discovery, Volume 2, Issue 4, Jun 2005, p. 302 - 306
DOI: https://doi.org/10.2174/1570180054038332
- Available online: 01 Jun 2005

Abstract

A novel series of nonradiolabeled, polyfluorinated phenyltropanes were developed containing three or more 19 F atoms/molecule in a magnetic resonance (MR) equivalent chemical environment to increase coherent MR signal characteristics. Competitive radioreceptor affinity assays of such compounds yielded nM affinity at dopamine (DAT) and serotonin (SERT) transporters in rat brain tissue. Compound 3b (MCL-314) at 50 μM gave a clear magnetic resonance spectroscopy signal, and 9 (MCL-319) yielded very high DAT potency and improved selectivity over SERT. Such compounds might potentially serve as MRI- or MRS-detectable index ligands for the dopamine transporter proteins, and preliminary observations call for further study of additional polyfluorinated phenyltropanes.

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2005-06-01

2025-05-29

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Article Type: Review Article

Keyword(s): dopamine transporter; magnetic resonance imaging; magnetic resonance spectroscopy; polyfluorophenyltropane

Development of Polyfluorophenyltropanes: Potential Probes for 19F Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) Assessments of the Dopamine Transporter

Abstract

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