化学
兴奋剂
对接(动物)
立体化学
效力
受体
药理学
苯并噻吩
类阿片
体外
生物化学
生物
医学
护理部
有机化学
噻吩
作者
Xiang Li,Zixing Yu,Jingchao Cheng,Fengxia Ren,Hongxin Jia,Tao Zhang,Weiguo Shi,Shiqiang Cui,Yanhao Guo,Jing Li,Yatong Zhang
出处
期刊:ChemMedChem
[Wiley]
日期:2022-10-28
卷期号:17 (24)
被引量:1
标识
DOI:10.1002/cmdc.202200416
摘要
Compounds that activate only the G-protein signalling pathway represent an effective strategy for making safer opioids. In the present study, we report the design, synthesis and evaluation of two classes of novel PZM21 derivatives containing the benzothiophene ring and biphenyl ring group respectively as biased μ-opioid receptor (μOR) agonists. The new compound SWG-LX-33 showed potent μOR agonist activity and produced μOR-dependent analgesia. SWG-LX-33 does not activate the β-arrestin-2 signalling pathway in vitro even at high concentrations. Computational docking demonstrated the amino acid residue ASN150 to be critical for the weak efficacy and potency of μOR agonists in arrestin recruitment.
科研通智能强力驱动
Strongly Powered by AbleSci AI