6-(5-chloro-3-formyl-2-hydroxyphenyl)-4-(2-chloro-5-(trifluoromethyl)phenyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | 931112-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-(5-chloro-3-formyl-2-hydroxyphenyl)-4-(2-chloro-5-(trifluoromethyl)phenyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile
• 英文别名: 6-(5-chloro-3-formyl-2-hydroxyphenyl)-4-[2-chloro-5-(trifluoromethyl)phenyl]-2-oxo-1H-pyridine-3-carbonitrile
• CAS: 931112-56-0
• 化学式: C₂₀H₉Cl₂F₃N₂O₃
• 分子量: 453.204
• InChiKey: FYAFNYIIDQETED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(5-chloro-3-formyl-2-hydroxyphenyl)-4-(2-chloro-5-(trifluoromethyl)phenyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile 在 sodium hydroxide 、 silver(l) oxide 作用下， 以 水 、 叔丁醇 为溶剂， 反应 24.0h， 生成 5-chloro-3-(4-(2-chloro-5-(trifluoromethyl)phenyl)-5-cyano-6-oxo-1,6-dihydropyridin-2-yl)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Survivin inhibitors

  摘要：

  抑制survivin的化合物、含有这些化合物的组合物以及治疗survivin失调或过度表达疾病的方法被揭示。

  公开号：

  US20070072833A1
• 作为产物：
  描述：

  6-(5-chloro-2-hydroxyphenyl)-4-(2-chloro-5-(trifluoromethyl)phenyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile 在 palladium diacetate 三乙基硅烷 、 1,1'-双(二苯基膦)二茂铁 、 N-碘代丁二酰亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 6-(5-chloro-3-formyl-2-hydroxyphenyl)-4-(2-chloro-5-(trifluoromethyl)phenyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile
  参考文献：
  名称：

  Discovery of a novel small molecule binding site of human survivin

  摘要：

  Survivin is one of the most tumor-specific genes in the human genome and is an attractive target for cancer therapy. However, small-molecule ligands for survivin have not yet been described. Thus, an interrogation of survivin which could potentially both validate a small-molecule therapy approach, and determine the biochemical nature of any of survivin's functions has not been possible. Here we describe the discovery and characterization of a small molecule binding site on the survivin surface distinct from the Smac peptide-binding site. The new site is located at the dimer interface and exhibits many of the features of highly druggable, biologically relevant protein binding sites. A variety of small hydrophobic compounds were found that bind with moderate affinity to this binding site, from which one lead was developed into a group of compounds with nanomolar affinity. Additionally, a subset of these compounds are adequately water-soluble and cell-permeable. Thus, the structural studies and small molecules described here provide tools that can be used to probe the biochemical role(s) of survivin, and may ultimately serve as a basis for the development of small molecule therapeutics acting via direct or allosteric disruption of binding events related to this poorly understood target. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.042

文献信息

• US7910742B2
  申请人：——

  公开号：US7910742B2

  公开（公告）日：2011-03-22
• Survivin inhibitors
  申请人：Wendt D. Michael

  公开号：US20070072833A1

  公开（公告）日：2007-03-29

  Compounds that inhibit survivin, compositions containing the compounds and methods of treating diseases in which survivin is unregulated or overexpressed are disclosed.

  抑制survivin的化合物、含有这些化合物的组合物以及治疗survivin失调或过度表达疾病的方法被揭示。
• Discovery of a novel small molecule binding site of human survivin
  作者：Michael D. Wendt、Chaohong Sun、Aaron Kunzer、Daryl Sauer、Kathy Sarris、Ethan Hoff、Liping Yu、David G. Nettesheim、Jun Chen、Sha Jin、Kenneth M. Comess、Yihong Fan、Steven N. Anderson、Binumol Isaac、Edward T. Olejniczak、Philip J. Hajduk、Saul H. Rosenberg、Steven W. Elmore

  DOI：10.1016/j.bmcl.2007.03.042

  日期：2007.6

  Survivin is one of the most tumor-specific genes in the human genome and is an attractive target for cancer therapy. However, small-molecule ligands for survivin have not yet been described. Thus, an interrogation of survivin which could potentially both validate a small-molecule therapy approach, and determine the biochemical nature of any of survivin's functions has not been possible. Here we describe the discovery and characterization of a small molecule binding site on the survivin surface distinct from the Smac peptide-binding site. The new site is located at the dimer interface and exhibits many of the features of highly druggable, biologically relevant protein binding sites. A variety of small hydrophobic compounds were found that bind with moderate affinity to this binding site, from which one lead was developed into a group of compounds with nanomolar affinity. Additionally, a subset of these compounds are adequately water-soluble and cell-permeable. Thus, the structural studies and small molecules described here provide tools that can be used to probe the biochemical role(s) of survivin, and may ultimately serve as a basis for the development of small molecule therapeutics acting via direct or allosteric disruption of binding events related to this poorly understood target. (C) 2007 Elsevier Ltd. All rights reserved.