化学
角色扮演
罗氟司特
药理学
血管性痴呆
IC50型
痴呆
酶
生物化学
内科学
体外
医学
磷酸二酯酶
疾病
慢性阻塞性肺病
作者
Jinhao Liang,Yi‐You Huang,Qian Zhou,Yuqi Gao,Zhe Li,Deyan Wu,Si Yu,Lei Guo,Zhen Chen,Ling Huang,Steven H. Liang,Xian-Hui He,Ruibo Wu,Hai‐Bin Luo
标识
DOI:10.1021/acs.jmedchem.0c00060
摘要
To validate PDE4 inhibitors as novel therapeutic agents against vascular dementia (VaD), 25 derivatives were discovered from the natural inhibitor α-mangostin (IC50 = 1.31 μM). Hit-to-lead optimization identified a novel and selective PDE4 inhibitor 4e (IC50 = 17 nM), which adopted a different binding pattern from PDE4 inhibitors roflumilast and rolipram. Oral administration of 4e at a dose of 10 mg/kg exhibited remarkable therapeutic effects in a VaD model and did not cause emesis to beagle dogs, indicating its potential as a novel anti-VaD agent.
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