2-[6-(4-Chlorophenoxy)-2-oxoacenaphthylen-1-ylidene]propanedinitrile | 1422531-70-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[6-(4-Chlorophenoxy)-2-oxoacenaphthylen-1-ylidene]propanedinitrile
• 英文别名: 2-[6-(4-chlorophenoxy)-2-oxoacenaphthylen-1-ylidene]propanedinitrile
• CAS: 1422531-70-1
• 化学式: C₂₁H₉ClN₂O₂
• 分子量: 356.768
• InChiKey: KYXYOAYQWRWUIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苊醌 在 溴 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 生成 2-[6-(4-Chlorophenoxy)-2-oxoacenaphthylen-1-ylidene]propanedinitrile
  参考文献：
  名称：

  Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach

  摘要：

  Based on a known nanomolar Bcl-2 homology domain 3 (BH3) mimetic 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b] pyrrole-9-carbonitrile (SI, MW: 331), we applied a fragment-based approach to obtain BH3 mimetics with improved affinity and improved solubility in a water ethanol (9:1) cosolvent. After the deconstruction of 1 (S1), we obtained fragment cyanoacetamide (4), which was determined to be a ligand efficiency (LE) hot part. After a rational optimization through fragment evolution beginning with fragment 4, a smaller Mcl-1 inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g, MW: 288) with a 6-fold increase in affinity compared to I was obtained, as predicted by our optimization curve and identified by Mcl-1 protein nuclear magnetic resonance (NMR). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.050

文献信息

• Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach
  作者：Zhichao Zhang、Ting Song、Xiangqian Li、Zhiyong Wu、Yingang Feng、Feibo Xie、Chengwu Liu、Jianquan Qin、Hongbo Chen

  DOI：10.1016/j.ejmech.2012.10.050

  日期：2013.1

  Based on a known nanomolar Bcl-2 homology domain 3 (BH3) mimetic 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b] pyrrole-9-carbonitrile (SI, MW: 331), we applied a fragment-based approach to obtain BH3 mimetics with improved affinity and improved solubility in a water ethanol (9:1) cosolvent. After the deconstruction of 1 (S1), we obtained fragment cyanoacetamide (4), which was determined to be a ligand efficiency (LE) hot part. After a rational optimization through fragment evolution beginning with fragment 4, a smaller Mcl-1 inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g, MW: 288) with a 6-fold increase in affinity compared to I was obtained, as predicted by our optimization curve and identified by Mcl-1 protein nuclear magnetic resonance (NMR). (C) 2012 Elsevier Masson SAS. All rights reserved.