(S,Z)-5-((1R,4R)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dienyl)cyclohexylamino)-5-oxopent-3-en-2-yl 4-(3-methoxyphenyl)piperazine-1-carboxylate | 1197054-32-2

• 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: (S,Z)-5-((1R,4R)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dienyl)cyclohexylamino)-5-oxopent-3-en-2-yl 4-(3-methoxyphenyl)piperazine-1-carboxylate
• CAS: 1197054-32-2
• 化学式: C₃₇H₅₃N₃O₆
• 分子量: 635.844
• InChiKey: QHWQWWOFRGKXEY-UWDGLTGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.19
• 重原子数：
  46.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  92.87
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  (S,Z)-5-(((1s,4s)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dien-1-yl)cyclohexyl)amino)-5-oxopent-3-en-2-yl(4-nitrophenyl)carbonate 、 1-(3-甲氧基苯基)哌嗪 以 1,2-二氯乙烷 为溶剂， 反应 1.25h， 以46%的产率得到(S,Z)-5-((1R,4R)-4-((2E,4E)-5-((3R,5S)-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-5-yl)-3-methylpenta-2,4-dienyl)cyclohexylamino)-5-oxopent-3-en-2-yl 4-(3-methoxyphenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthetic mRNA Splicing Modulator Compounds with in Vivo Antitumor Activity

  摘要：

  We report our progress on the development of new synthetic anticancer lead compounds that modulate the splicing of mRNA, We also report the synthesis and evaluation of new biologically active ester and carbamate analogues. Further, we describe initial animal studies demonstrating the antitumor efficacy of compound 5 in vivo. Additionally, we report the enantioselective and diastereospecific synthesis of a new 1,3-dioxane series of active analogues, We confirm that compound 5 inhibits the splicing of mRNA in cell-free nuclear extracts and in a cell-based dual-reporter mRNA splicing assay. In summary, we have developed totally synthetic novel spliceosome modulators as therapeutic lead compounds for a number or highly aggressive cancers. Future efforts will be directed toward the more complete optimization of these compounds as potential human therapeutics.

  DOI：

  10.1021/jm901215m

文献信息

• ANTICANCER COMPOUNDS AND METHODS OF MAKING AND USING SAME
  申请人：Webb Thomas R.

  公开号：US20110178098A1

  公开（公告）日：2011-07-21

  In one aspect, the invention relates to compounds having anticancer activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with uncontrolled cellular proliferation using the compounds and compositions. This abstract is intended to be used as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及具有抗癌活性的化合物；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与细胞不受控制增殖相关的疾病的方法。本摘要旨在用作扫描工具，用于在特定领域进行搜索，并不意味着对本发明的限制。
• US8969405B2
  申请人：——

  公开号：US8969405B2

  公开（公告）日：2015-03-03
• [EN] ANTICANCER COMPOUNDS AND METHODS OF MAKING AND USING SAME<br/>[FR] COMPOSÉS ANTICANCÉREUX ET PROCÉDÉS DE FABRICATION ET D'UTILISATION CORRESPONDANTS
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2009155606A1

  公开（公告）日：2009-12-23

  In one aspect, the invention relates to compounds having anticancer activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders associated with uncontrolled cellular proliferation using the compounds and compositions. This abstract is intended to be used as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
• Synthetic mRNA Splicing Modulator Compounds with in Vivo Antitumor Activity
  作者：Chandraiah Lagisetti、Alan Pourpak、Tinopiwa Goronga、Qin Jiang、Xiaoli Cui、Judith Hyle、Jill M. Lahti、Stephan W. Morris、Thomas R. Webb

  DOI：10.1021/jm901215m

  日期：2009.11.26

  We report our progress on the development of new synthetic anticancer lead compounds that modulate the splicing of mRNA, We also report the synthesis and evaluation of new biologically active ester and carbamate analogues. Further, we describe initial animal studies demonstrating the antitumor efficacy of compound 5 in vivo. Additionally, we report the enantioselective and diastereospecific synthesis of a new 1,3-dioxane series of active analogues, We confirm that compound 5 inhibits the splicing of mRNA in cell-free nuclear extracts and in a cell-based dual-reporter mRNA splicing assay. In summary, we have developed totally synthetic novel spliceosome modulators as therapeutic lead compounds for a number or highly aggressive cancers. Future efforts will be directed toward the more complete optimization of these compounds as potential human therapeutics.