Azologization of Serotonin 5-HT Receptor Antagonists

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2019 Apr 18

PMID 30992726

Citations 4

Authors

Karin Rustler

Galyna Maleeva

Piotr Bregestovski

Burkhard Konig

Affiliations

Soon will be listed here.

Abstract

The serotonin 5-hydroxytryptamine 3 receptor (5-HTR) 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-HT 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-HTR antagonists. Despite reported proof of principle of direct azologization, only one of the investigated derivatives showed antagonistic activity lacking isomer specificity.

Citing Articles

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Photopharmacology of Ion Channels through the Light of the Computational Microscope.

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Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors.

Grathwol C, Wossner N, Swyter S, Smith A, Tapavicza E, Hofstetter R Beilstein J Org Chem. 2019; 15:2170-2183.

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