Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5

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• 作者：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
• 关键词：PDE5 inhibitors ; 5-Bromopyrimidin-4(3H)-ones
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：23
• 期：17
• 页码：4944-4947
• 全文大小：2158 K

文摘

The substituents both at the 6-position of the 5-bromopyrimidinone ring and at the 5¡ä-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 5¡ä-position of the phenyl ring of 5-bormopyrimidinones and the resulted compound 13a has the highest inhibition activity to PDE5 (IC₅₀, 1.7 nM).