Cao Yangzhi, Shi Shuang, Does Simone A H, Buzink Christian M L, Gao Meichun, de Esch Iwan J P, Vischer Henry F, Wijtmans Maikel, Leurs Rob
Division of Medicinal Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.
J Med Chem. 2025 Jun 26;68(12):12911-12924. doi: 10.1021/acs.jmedchem.5c00792. Epub 2025 Jun 10.
Clenbuterol is a potent partial agonist on the human β-adrenergic receptor (β-AR) and available for veterinary use to treat respiratory diseases. We executed an "" strategy to generate a small library of photoresponsive azobenzene derivatives of clenbuterol. Illumination with two complementary wavelengths allowed interconversion between isomeric and forms, as proven by UV/vis, NMR and LC-MS studies. The photoswitchable clenbuterol analogs were pharmacologically characterized using β-AR radioligand binding and cAMP assays. Key compound (VUF26034) has suitable photochemical properties and good thermal stability of the isomer ( ∼ 4 months), switching from a partial agonist to a >25-fold higher affinity antagonist upon illumination with 360 nm.
克仑特罗是一种对人β-肾上腺素能受体（β-AR）有强效的部分激动剂，可用于兽医治疗呼吸道疾病。我们实施了一种“”策略，以生成一个克仑特罗的光响应性偶氮苯衍生物的小型文库。如紫外可见光谱、核磁共振和液相色谱-质谱研究所示，用两种互补波长照射可使异构体和形式之间相互转换。使用β-AR放射性配体结合和环磷酸腺苷测定对可光开关的克仑特罗类似物进行了药理学表征。关键化合物（VUF26034）具有合适的光化学性质和异构体良好的热稳定性（约4个月），在用36 nm照射时从部分激动剂转变为亲和力高25倍以上的拮抗剂。
