化学
对抗
TRPV1型
乙酰胺
敌手
立体化学
体内
结构-活动关系
止痛药
化学合成
生物活性
药理学
体外
受体
生物化学
有机化学
瞬时受体电位通道
生物技术
生物
医学
作者
Jin Mi Kang,Sun Ok Kwon,Jihyae Ann,Sunho Lee,Changhoon Kim,Nayeon Do,Jin Ju Jeong,Peter M. Blumberg,Hee-Jin Ha,Thi Ngoc Lan Vu,Sanghee Yoon,Sun Choi,Robert Frank-Foltyn,B. Lesch,Gregor Bahrenberg,Hannelore Stockhausen,Thomas Christoph,Jeeyeon Lee
标识
DOI:10.1016/j.bmcl.2021.128266
摘要
A series consisting of 117 2-(halogenated phenyl) acetamide and propanamide analogs were investigated as TRPV1 antagonists. The structure-activity analysis targeting their three pharmacophoric regions indicated that halogenated phenyl A-region analogs exhibited a broad functional profile ranging from agonism to antagonism. Among the compounds, antagonists 28 and 92 exhibited potent antagonism toward capsaicin for hTRPV1 with Ki[CAP] = 2.6 and 6.9 nM, respectively. Further, antagonist 92 displayed promising analgesic activity in vivo in both phases of the formalin mouse pain model. A molecular modeling study of 92 indicated that the two fluoro groups in the A-region made hydrophobic interactions with the receptor.
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