Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception

Autor:	Siyu Song, Xiangshuo Ouyang, Dengqi Xue, KeWei Wang, Heling Niu, Liying Dong, Yani Liu, Liming Shao, Denggao Zhang, Yilin Zheng, Qianwei Ge
Rok vydání:	2022
Předmět:	SNi Chemistry Ralfinamide Neuropathic pain medicine Potency General Chemistry Nerve injury medicine.symptom Pharmacology Inhibitory postsynaptic potential IC50 Open field
Zdroj:	Chinese Chemical Letters. 33:1643-1646
ISSN:	1001-8417
Popis:	Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide, and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration (IC50) values ranging from 2.9 µmol/L to 21.4 µmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy to improve the Nav1.7 inhibition of ralfinamide analogues. Compound 19h was efficacious in antinociception in the mouse spared nerve injury (SNI) model of neuropathic pain without causing sedation in the open field test.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::d87ffe13959837c81ec6efdc5ce4d01d https://doi.org/10.1016/j.cclet.2021.08.026 Zobrazit plný text záznamu Full Text from ScienceDirect