Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595451 | Bioorganic & Medicinal Chemistry Letters | 2013 | 4 Pages |
Abstract
The substituents both at the 6-position of the 5-bromopyrimidinone ring and at the 5â²-position of the phenyl ring of 5-bromopyrimidin-4(3H)-ones were explored. 5-Bromo-6-isopropyl-2-(2-propoxy-phenyl)pyrimidin-4(3H)-one was identified as a new scaffold for potent PDE5 inhibitors. The crystal structures of PDE5/2e and PDE5/10a complexes provided a structural basis for the inhibition of 5-bromopyrimidinones to PDE5. In addition, it was also found that there is a great tolerance for the substitution at the 5â²-position of the phenyl ring of 5-bormopyrimidinones and the resulted compound 13a has the highest inhibition activity to PDE5 (IC50, 1.7Â nM).
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Xudong Gong, Guan Wang, Jing Ren, Zheng Liu, Zhen Wang, Tiantian Chen, Xiaojun Yang, Xiangrui Jiang, Jingshan Shen, Hualiang Jiang, Haji Akber Aisa, Yechun Xu, Jianfeng Li,