Synthesis and in vitro evaluation of novel derivatives of diphenylsulfide as serotonin transporter ligands.
As the serotonin transporter (SERT) is involved in several neurodegenerative and psychiatric disorders, radiopharmaceuticals to image the SERT by PET or SPECT would be very valuable in studying these diseases. For the development of imaging agents, we have synthesized novel derivatives of recently reported diphenylsulfide SERT ligands, in which the sulfur atom linking the two phenyl rings was replaced by an oxygen, sulfinyl, sulfonyl, amino or carbon group. Three of these exhibited good to high in vitro affinity (0.5 nM < K(i) < 11 nM) and selectivity for the SERT over the other monoamine transporters.
Vercouillie
Johnny
J
Université François Rabelais de Tours, INSERM U619, Laboratoire de Biophysique Médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France.
Mavel
Sylvie
S
Galineau
Laurent
L
Ragusa
Tiziana
T
Innis
Robert
R
Kassiou
Michael
M
Chalon
Sylvie
S
Dollé
Frédéric
F
Besnard
Jean-Claude
JC
Guilloteau
Denis
D
Emond
Patrick
P
D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D008024:Ligands; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides