Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists
Abstract‘Biased’ ligands of G protein-coupled receptors (GPCRs) represent a type of promising analgesic with reduced on-target side effects. PZM21, a potent μ-opioid-receptor (μOR)-biased agonist with a new chemical scaffold compared to classic opioids, has been identified as a therapeutic lead molecule for treating pain. In the current study, novel PZM21 analogues were synthesized and evaluated for their in vitro and in vivo efficacy. Novel compound 7a and PZM21 demonstrated undetectable β-arrestin-2 recruitment, however, their analgesic effects need to be further confirmed. Compounds 7b, 7d, and 7g were stronger analgesics than PZM21 in both the mouse formalin injection assay and the writhing test. Compound 7d was the most potent analogue, requiring a dose that was 1/16th to 1/4th of that of PZM21 for its analgesic activity in the two assays, respectively. Therefore, compound 7d could serve as a lead to develop new biased μOR agonists for treating pain. View Full-Text
Share & Cite This Article
Ma, M.; Sun, J.; Li, M.; Yu, Z.; Cheng, J.; Zhong, B.; Shi, W. Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists. Molecules 2019, 24, 259.
Ma M, Sun J, Li M, Yu Z, Cheng J, Zhong B, Shi W. Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists. Molecules. 2019; 24(2):259.Chicago/Turabian Style
Ma, Mengjun; Sun, Jialin; Li, Menghua; Yu, Zixing; Cheng, Jingchao; Zhong, Bohua; Shi, Weiguo. 2019. "Synthesis and Evaluation of Novel Biased μ-Opioid-Receptor (μOR) Agonists." Molecules 24, no. 2: 259.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.