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 < Ki < 11 nM) and selectivity for the SERT over the other monoamine transporters.

Graphical abstractA series of diphenylsulfide derivatives was prepared and their binding affinities for monoamine transporters (SERT, DAT, and NET) are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide