de-allyl PAC-1 | 315183-08-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: de-allyl PAC-1
• 英文别名: 2-(4-benzylpiperazin-1-yl)-N-[(2-hydroxyphenyl)methylideneamino]acetamide
• CAS: 315183-08-5
• 化学式: C₂₀H₂₄N₄O₂
• mdl: MFCD02075048
• 分子量: 352.436
• InChiKey: VPOFFCAWPSKAPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-苄基-4-(乙氧基羰基甲基)哌嗪 在 盐酸 、 肼 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 1.5h， 生成 de-allyl PAC-1
  参考文献：
  名称：

  WO2008/134474

  摘要：

  公开号：

文献信息

• Parallel Synthesis and Biological Evaluation of 837 Analogues of Procaspase-Activating Compound 1 (PAC-1)
  作者：Danny C. Hsu、Howard S. Roth、Diana C. West、Rachel C. Botham、Chris J. Novotny、Steven C. Schmid、Paul J. Hergenrother

  DOI：10.1021/co2001372

  日期：2012.1.9

  Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3.
• WO2008/134474
  申请人：——

  公开号：——

  公开（公告）日：——