biostudies-literatureRodriguez-Soacha DAElitenetzwerk BayernDeutscher Akademischer AustauschdienstNational Institute on Alcohol Abuse and AlcoholismDeutsche ForschungsgemeinschaftNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNIDA NIH HHSNIAAA NIH HHSEuropean Cooperation in Science and TechnologyNational Institute on Drug Abuse1632-1647https://www.ebi.ac.uk/biostudies/studies/S-EPMC9016771biostudies-literatureUnknown12(9)Human cannabinoid receptor type 1 (<i>h</i>CB₁R) plays important roles in the regulation of appetite and development of addictive behaviors. Herein, we describe the design, synthesis, photocharacterization, molecular docking, and <i>in vitro</i> characterization of "photo-rimonabant", i.e., azo-derivatives of the selective <i>h</i>CB₁R antagonist SR1411716A (rimonabant). By applying azo-extension strategies, we yielded compound <b>16a</b>, which shows marked affinity for CB₁R (<i>K</i>_{i (<i>cis</i> form)} = 29 nM), whose potency increases by illumination with ultraviolet light (CB₁R K_i<i>trans</i>/<i>cis</i> ratio = 15.3). Through radioligand binding, calcium mobilization, and cell luminescence assays, we established that <b>ACS chemical neuroscience"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar "<i>Cis</i>-On" CB₁R Antagonist.PMC9016771AA023256DFG DE1546/10-1CA15135 (MuTaLiG)U18 DA052495R01 DK124615R01 AA022235DK124615R01 DK100414R01 DK103625PhD scholarshipDA052495International Doctoral Program &quot;Receptor Dynamics&quot;Sotriffer CFender JLorenz KCollado JARodriguez-Soacha DAMaitra RDecker MRamirez YAMunoz Efalse"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar "<i>Cis</i>-On" CB₁R Antagonist.Human cannabinoid receptor type 1 (<i>h</i>CB₁R) plays important roles in the regulation of appetite and development of addictive behaviors. Herein, we describe the design, synthesis, photocharacterization, molecular docking, and <i>in vitro</i> characterization of "photo-rimonabant", i.e., azo-derivatives of the selective <i>h</i>CB₁R antagonist SR1411716A (rimonabant). By applying azo-extension strategies, we yielded compound <b>16a</b>, which shows marked affinity for CB₁R (<i>K</i>_{i (<i>cis</i> form)} = 29 nM), whose potency increases by illumination with ultraviolet light (CB₁R K_i<i>trans</i>/<i>cis</i> ratio = 15.3). Through radioligand binding, calcium mobilization, and cell luminescence assays, we established that <b>2021-01-01T00:00:00Z2021 May2026-05-09T17:31:25.887Z2024-11-15T12:40:07.105ZS-EPMC90167713385676410.1021/acschemneuro.1c00086