cyclohexyl pyrrolidine-1-carbo(dithioperoxo)thioate | 42267-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: cyclohexyl pyrrolidine-1-carbo(dithioperoxo)thioate
• 英文别名: Cyclohexylsulfanyl pyrrolidine-1-carbodithioate
• CAS: 42267-46-9
• 化学式: C₁₁H₁₉NS₃
• 分子量: 261.477
• InChiKey: UDUVLNUAVDWVCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  85.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  环己硫醇 、 bis-(pyrrolidine-1-thiocarbonyl)-disulfane 以 乙醇 为溶剂， 反应 16.0h， 以13%的产率得到cyclohexyl pyrrolidine-1-carbo(dithioperoxo)thioate
  参考文献：
  名称：

  Exploring the Structural Requirements for Inhibition of the Ubiquitin E3 Ligase Breast Cancer Associated Protein 2 (BCA2) as a Treatment for Breast Cancer

  摘要：

  The zinc-ejecting aldehyde dehydrogenase (A LDH) inhibitory drug disulfiram (DS F) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C=S)S-S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC(50)) in BCA2 positive MCF-7 and T47D cells but were inactive (IC(50)> 10 mu M) in BCA2 negative M DA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve M DA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.

  DOI：

  10.1021/jm901757t

文献信息

• [EN] ANTI-CANCER THERAPEUTIC AGENTS<br/>[FR] AGENTS THÉRAPEUTIQUES ANTICANCÉREUX
  申请人：UNIV WAYNE STATE

  公开号：WO2011097218A1

  公开（公告）日：2011-08-11

  There is provided the use of disulfiram and analogs thereof to inhibit catalytic activity. Additionally, dithioperoxothioates can be used to inhibit catalytic activity. More specifically, the present invention is utilized to inhibit the catalytic activity of ubiquitin E3 ligase BCA2 for treating cancer.
• Exploring the Structural Requirements for Inhibition of the Ubiquitin E3 Ligase Breast Cancer Associated Protein 2 (BCA2) as a Treatment for Breast Cancer
  作者：Ghali Brahemi、Fathima R. Kona、Annalisa Fiasella、Daniela Buac、Jitka Soukupová、Andrea Brancale、Angelika M. Burger、Andrew D. Westwell

  DOI：10.1021/jm901757t

  日期：2010.4.8

  The zinc-ejecting aldehyde dehydrogenase (A LDH) inhibitory drug disulfiram (DS F) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C=S)S-S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC(50)) in BCA2 positive MCF-7 and T47D cells but were inactive (IC(50)> 10 mu M) in BCA2 negative M DA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve M DA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.