Tsuchiya Keisuke, Umeno Tomohiro, Tsuji Genichiro, Yokoo Hidetomo, Tanaka Masakazu, Fukuhara Kiyoshi, Demizu Yosuke, Misawa Takashi
Graduate School of Pharmacy, Showa University.
National Institute of Health Sciences.
Chem Pharm Bull (Tokyo). 2020;68(4):398-402. doi: 10.1248/cpb.c19-01108.
Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on their conformational change by photo-irradiation. Previously, we have reported several types of selective estrogen receptor (ER) modulators based on diphenylmethane skeleton. To develop novel photopharmacological reagents, we designed and synthesized a set of ER ligands based on azobenzene skeleton, which can switch its conformation following UV irradiation. Our results showed that after UV irradiation, the Z-form of the synthesized compound 9 interacted with ERα, with a K value of 2.5 µM, whereas the E-form of compound 9 did not bind ability to ERα at 10 µM.
光药理学作为一种新型治疗方法的开发途径已引起关注，因为它能够通过光照射基于化合物的构象变化来调节其生物活性。此前，我们已经报道了几种基于二苯甲烷骨架的选择性雌激素受体（ER）调节剂。为了开发新型光药理学试剂，我们设计并合成了一组基于偶氮苯骨架的ER配体，其在紫外线照射后可改变构象。我们的结果表明，紫外线照射后，合成化合物9的Z型与ERα相互作用，K值为2.5µM，而化合物9的E型在10µM时对ERα没有结合能力。
