将氮原子引入酰胺基烷基吲哚：具有增强水溶性的强效且选择性的大麻素2型受体激动剂。
Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility.
作者信息
Ji Yue-Yang, Wang Zhi-Long, Pei Fang-Ning, Shi Jun-Jie, Li Jiao-Jiao, Gunosewoyo Hendra, Yang Fan, Tang Jie, Xie Xin, Yu Li-Fang
机构信息
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development , School of Chemistry and Molecular Engineering , East China Normal University , 3663 North Zhongshan Road , Shanghai 200062 , China . Email:
CAS Key Laboratory of Receptor Research , National Center for Drug Screening , Shanghai Institute of Materia Medica , Chinese Academy of Sciences , 189 Guo Shou Jing Road , Shanghai 201203 , China . Email:
出版信息
Medchemcomm. 2019 Nov 18;10(12):2131-2139. doi: 10.1039/c9md00411d. eCollection 2019 Dec 1.
Abstract
Previously we identified a series of amidoalkylindoles as potent and selective CB partial agonists. In the present study, we report our continuous effort to improve the aqueous solubility by introducing N atoms to the amidoalkylindole framework. Synthesis, characterization, and pharmacology evaluations were described. Bioisosteric replacements of the indole nucleus with an indazole, azaindole and benzimidazole were explored. Benzimidazole (EC = NA, EC = 0.067 μM) and azaindole (EC = NA, EC = 0.048 μM) were found to be potent and selective CB receptor partial agonists, both with improved aqueous solubility.
摘要
此前我们鉴定出一系列氨基烷基吲哚为强效且选择性的CB部分激动剂。在本研究中，我们报告了我们通过在氨基烷基吲哚骨架中引入氮原子来提高水溶性的持续努力。描述了合成、表征和药理学评价。探索了用吲唑、氮杂吲哚和苯并咪唑对吲哚核进行生物电子等排体替换。发现苯并咪唑（EC = NA，EC = 0.067 μM）和氮杂吲哚（EC = NA，EC = 0.048 μM）是强效且选择性的CB受体部分激动剂，二者水溶性均有所提高。
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