化学
变构调节
变构调节剂
脉冲前抑制
烟碱激动剂
毒蕈碱乙酰胆碱受体
乙酰胆碱受体
噻唑
增强剂
酰胺
羧酸
立体化学
受体
药理学
神经科学
生物化学
精神分裂症(面向对象编程)
心理学
医学
精神科
作者
Chunfang Yang,Ying Meng,Xintong Wang,Xin Li,Ting Yu,Weiming Liao,Wenjun Xie,Qianchen Jiang,Han Wang,Shan Cheng,Wenxuan Jiao,Xue-Bin Bian,Fang Hu,Xiaowei Wang,Yani Liu,Liangren Zhang,KeWei Wang,Qi Sun
标识
DOI:10.1021/acs.jmedchem.3c02323
摘要
Enhancing α7 nAChR function serves as a therapeutic strategy for cognitive disorders. Here, we report the synthesis and evaluation of 2-arylamino-thiazole-5-carboxylic acid amide derivatives 6–9 that as positive allosteric modulators (PAMs) activate human α7 nAChR current expressed in Xenopus ooctyes. Among the 4-amino derivatives, a representative atypical type I PAM 6p exhibits potent activation of α7 current with an EC50 of 1.3 μM and the maximum activation effect on the current over 48-fold in the presence of acetylcholine (100 μM). The structure–activity relationship (SAR) analysis reveals that the 4-amino group is crucial for the allosteric activation of α7 currents by compound 6p as the substitution of 4-methyl group results in its conversion to compound 7b (EC50 = 2.1 μM; max effect: 58-fold) characterized as a typical type I PAM. Furthermore, both 6p and 7b are able to rescue auditory gating deficits in mouse schizophrenia-like model of acoustic startle prepulse inhibition.
科研通智能强力驱动
Strongly Powered by AbleSci AI