Design and synthesis of (2R,3S)-iodoreboxetine analogues for SPECT imaging of the noradrenaline transporter.
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.
Jobson
Nicola K
NK
WestCHEM, Department of Chemistry, University of Glasgow, Glasgow, UK.
Crawford
Andrew R
AR
Dewar
Deborah
D
Pimlott
Sally L
SL
Sutherland
Andrew
A
D015195:Drug Design; D007457:Iodine Radioisotopes / Q000737:chemistry; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D000077593:Reboxetine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D000077593:Reboxetine