5-iodo-6-ethyl-2-[2-n-propoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]pyrimid-4(3H)-one | 1229019-28-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-iodo-6-ethyl-2-[2-n-propoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]pyrimid-4(3H)-one
• 英文别名: 6-Ethyl-5-Iodo-2-{5-[(4-Methylpiperazin-1-Yl)sulfonyl]-2-Propoxyphenyl}pyrimidin-4(3h)-One；4-ethyl-5-iodo-2-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-1H-pyrimidin-6-one
• CAS: 1229019-28-6
• 化学式: C₂₀H₂₇IN₄O₄S
• 分子量: 546.429
• InChiKey: CLYYLXSJJMHCHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-丙氧基苯甲腈 在 氯磺酸 、 碘 、 potassium carbonate 、 silver nitrate 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.67h， 生成 5-iodo-6-ethyl-2-[2-n-propoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]pyrimid-4(3H)-one
  参考文献：
  名称：

  Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors

  摘要：

  For proof-of-concept of halogen bonding in drug design, a series of halogenated compounds were designed based on a lead structure as new inhibitors of phosphodiesterase type S. Bioassay results revealed a good correlation between the measured bioactivity and the calculated halogen bond energy. Our X-ray crystal structures verified the existence of the predicted halogen bonds, demonstrating that the halogen bond is an applicable tool in drug design and should be routinely considered in lead optimization.

  DOI：

  10.1021/jm200644r

文献信息

• PHENYL PYRIMIDONE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, PREPARATION METHODS AND USES THEREOF
  申请人：Topharman Shanghai Co., Ltd.

  公开号：EP2383262B1

  公开（公告）日：2016-07-06
• Design, Synthesis, and Pharmacological Evaluation of Monocyclic Pyrimidinones as Novel Inhibitors of PDE5
  作者：Guan Wang、Zheng Liu、Tiantian Chen、Zhen Wang、Huaiyu Yang、Mingyue Zheng、Jing Ren、Guanghui Tian、Xiaojun Yang、Li Li、Jianfeng Li、Jin Suo、Rongxia Zhang、Xiangrui Jiang、Nicholas Kenneth Terrett、Jingshan Shen、Yechun Xu、Hualiang Jiang

  DOI：10.1021/jm301159y

  日期：2012.12.13

  Cyclic nucleotide phosphodiesterase type 5 (PDES) is a prime drug target for treating the diseases associated with a lower level of the cyclic guanosine monophosphate (cGMP), which is a specific substrate for PDE5 hydrolysis. Here we report a series of novel PDE5 inhibitors with the new scaffold of the monocyclic pyrimidin-4(3H)-one ring developed using the structure-based discovery strategy. In total, 37 derivatives of the pyrimidin-4(3H)-ones, were designed, synthesized, and evaluated for their inhibitory activities to PDES, resulting in 25 compounds with IC50 ranging from 1 to 100 nM and 11 compounds with IC50 ranging from 1 to 10 nM. Compound 5, 5,6-diethyl-2[2-n-propoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]pyrimid-4(3H)-one, the most potent compound, has an excellent IC50 (1.6 nM) in vitro and a good efficacy in a rat model of erection. It thus provides a potential candidate for the further development into a new drug targeting PDE5.
• US8871777B2
  申请人：——

  公开号：US8871777B2

  公开（公告）日：2014-10-28
• Utilization of Halogen Bond in Lead Optimization: A Case Study of Rational Design of Potent Phosphodiesterase Type 5 (PDE5) Inhibitors
  作者：Zhijian Xu、Zheng Liu、Tong Chen、TianTian Chen、Zhen Wang、Guanghui Tian、Jing Shi、Xuelan Wang、Yunxiang Lu、Xiuhua Yan、Guan Wang、Hualiang Jiang、Kaixian Chen、Shudong Wang、Yechun Xu、Jingshan Shen、Weiliang Zhu

  DOI：10.1021/jm200644r

  日期：2011.8.11

  For proof-of-concept of halogen bonding in drug design, a series of halogenated compounds were designed based on a lead structure as new inhibitors of phosphodiesterase type S. Bioassay results revealed a good correlation between the measured bioactivity and the calculated halogen bond energy. Our X-ray crystal structures verified the existence of the predicted halogen bonds, demonstrating that the halogen bond is an applicable tool in drug design and should be routinely considered in lead optimization.