Design and synthesis of (2R,3S)-iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter

Nicola K Jobson; Andrew R Crawford; Deborah Dewar; Sally L Pimlott; Andrew Sutherland

doi:10.1016/j.bmcl.2009.07.064

Design and synthesis of (2R,3S)-iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter

Bioorg Med Chem Lett. 2009 Sep 1;19(17):4996-8. doi: 10.1016/j.bmcl.2009.07.064. Epub 2009 Jul 16.

Authors

Nicola K Jobson¹, Andrew R Crawford, Deborah Dewar, Sally L Pimlott, Andrew Sutherland

Affiliation

¹ WestCHEM, Department of Chemistry, University of Glasgow, Glasgow, UK.

PMID: 19640707
DOI: 10.1016/j.bmcl.2009.07.064

Abstract

A stereoselective 10-step synthesis of iodophenoxy analogues of (2R,3S)-reboxetine has been developed with the aim of generating a new SPECT imaging agent for the noradrenaline transporter (NAT). In vitro testing of these compounds against various mono-amine transporters showed an ortho-iodophenoxy analogue to have excellent affinity (K(i) 8.4 nM) and good selectivity for NAT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Design
Iodine Radioisotopes / chemistry
Morpholines / chemical synthesis*
Morpholines / chemistry
Norepinephrine Plasma Membrane Transport Proteins / analysis*
Norepinephrine Plasma Membrane Transport Proteins / metabolism
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / chemistry
Reboxetine
Stereoisomerism
Structure-Activity Relationship
Tomography, Emission-Computed, Single-Photon*

Substances

Iodine Radioisotopes
Morpholines
Norepinephrine Plasma Membrane Transport Proteins
Radiopharmaceuticals
Reboxetine

Grants and funding

Biotechnology and Biological Sciences Research Council/United Kingdom