Azologization of serotonin 5-HT3 receptor antagonists

Beilstein Journal of Organic Chemistry

Galyna Maleeva¹  Piotr Bregestovski¹  Karin Rustler²  Burkhard König² 

[1] Aix-Marseille University, INSERM, INS, Institut de Neurosciences des Systèmes, 13005 Marseille, France;Institute of Organic Chemistry, University of Regensburg, 93053 Regensburg, Germany;

关键词: azobenzene;    5-HT3R;    ion currents;    photopharmacology;    serotonin;   

DOI  :  10.3762/bjoc.15.74

来源: DOAJ

【 摘 要 】

The serotonin 5-hydroxytryptamine 3 receptor (5-HT3R) plays a unique role within the seven classes of the serotonin receptor family, as it represents the only ionotropic receptor, while the other six members are G protein-coupled receptors (GPCRs). The 5-HT3 receptor is related to chemo-/radiotherapy provoked emesis and dysfunction leads to neurodevelopmental disorders and psychopathologies. Since the development of the first serotonin receptor antagonist in the early 1990s, the range of highly selective and potent drugs expanded based on various chemical structures. Nevertheless, on-off-targeting of a pharmacophore’s activity with high spatiotemporal resolution as provided by photopharmacology remains an unsolved challenge bearing additionally the opportunity for detailed receptor examination. In the presented work, we summarize the synthesis, photochromic properties and in vitro characterization of azobenzene-based photochromic derivatives of published 5-HT3R antagonists. Despite reported proof of principle of direct azologization, only one of the investigated derivatives showed antagonistic activity lacking isomer specificity.

【 授权许可】

Unknown