化学
兴奋剂
选择性
四唑
对映体
体内
化学合成
结构-活动关系
立体化学
效力
药理学
体外
组合化学
生物化学
受体
医学
生物
生物技术
催化作用
作者
Xiaowen Peng,Christopher J. Holler,Anna-Maria F. Alves,Michelle G. Oliviera,Michael Speake,Angelo Pugliese,Mina Raeisolsadati Oskouei,Isabel Freitas,Angela Y.-P. Chen,Richard Gallegos,Stephanie M. McTighe,Gerhard Koenig,Raymond S Hurst,Jean‐François Blain,James C. Lanter,Duane A. Burnett
标识
DOI:10.1016/j.bmcl.2023.129595
摘要
Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies. SAR studies on conformationally locked macrocyclic analogs further improved the TRPML1 agonist potency while retaining the selectivity.
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