Structure-based design, synthesis, and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors
Structure-based design, synthesis, and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors
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作为 PDE9 抑制剂的新型嘧啶酮衍生物的基于结构的设计、合成和生物学评价
DOI：
10.1016/j.apsb.2017.12.007
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发表时间：
2018-07-01
影响因子：
14.5
通讯作者：
Luo, Hai-Bin
中科院分区：
文献类型：
--
作者：
Wu, Xu-Nian;Huang, Ya-Dan;Luo, Hai-Bin
阿尔茨海默病和2型糖尿病的病理过程已被证明是联系在一起的。PDE9抑制剂和PPAR γ激动剂如罗格列酮对这两种疾病均表现出显著的临床前和临床治疗效果。本研究发现了一系列结合罗格列酮药效团的PDE9抑制剂。所有化合物对PDE9都有明显的亲和力，其中4个化合物的IC_（50
The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPAR gamma agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC50 values