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General design and concept of bidirectional photoswitchable H3R antagonists. In this SAR study, the azobenzene moiety is incorporated in the core of compound 1 to give a series of differently substituted trans isomers (cyan). Illumination leads to their corresponding cis isomers (magenta). Within this study, we aimed to discover photoswitchable H3R antagonists that show at least a 10-fold increase or decrease in GPCR affinity upon illumination.
