tert-butyl 4-[[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-tritylsulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]methyl]imidazole-1-carboxylate | 1621326-00-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: tert-butyl 4-[[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-tritylsulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]methyl]imidazole-1-carboxylate
• CAS: 1621326-00-8
• 化学式: C₄₆H₄₈N₆O₆S₃
• 分子量: 877.122
• InChiKey: JUDRENNLJLUFPD-QEBRQXOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  61
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  233
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-tritylsulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]methyl]imidazole-1-carboxylate 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以44%的产率得到tert-butyl 4-[[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-sulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]methyl]imidazole-1-carboxylate
  参考文献：
  名称：

  Evaluation of class I HDAC isoform selectivity of largazole analogues

  摘要：

  Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, a series of analogues with modifications in the valine or the linker region were prepared and evaluated for their class I isoform selectivity. The inhibition profile showed that the C2 position of largazole has an optimal steric requirement for efficient HDAC inhibition and that substitution of the trans-alkene in the linker with an aromatic group results in complete loss of activity. This data will aid the design of class I isoform selective HDAC inhibitors.

  DOI：

  10.1016/j.bmcl.2014.07.006
• 作为产物：
  描述：

  在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以14.6 mg的产率得到tert-butyl 4-[[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-tritylsulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]methyl]imidazole-1-carboxylate
  参考文献：
  名称：

  Evaluation of class I HDAC isoform selectivity of largazole analogues

  摘要：

  Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, a series of analogues with modifications in the valine or the linker region were prepared and evaluated for their class I isoform selectivity. The inhibition profile showed that the C2 position of largazole has an optimal steric requirement for efficient HDAC inhibition and that substitution of the trans-alkene in the linker with an aromatic group results in complete loss of activity. This data will aid the design of class I isoform selective HDAC inhibitors.

  DOI：

  10.1016/j.bmcl.2014.07.006

文献信息

• MACROCYCLIC COMPOUNDS AND METHODS OF TREATMENT
  申请人：University of Florida Research Foundation, Inc.

  公开号：US20170197988A1

  公开（公告）日：2017-07-13

  The instant invention describes macrocyclic compounds having therapeutic activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders.
• US9815852B2
  申请人：——

  公开号：US9815852B2

  公开（公告）日：2017-11-14