octanedioic acid [4-(3-nitro-phenyl)thiazol-2-yl]amide | 944457-63-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: octanedioic acid [4-(3-nitro-phenyl)thiazol-2-yl]amide
• 英文别名: octanedioic acid [4-(3-nitro-phenyl)-thiazoI-2-yl]-amide；octanedioic acid [4-(3-Nitro-phenyl)-thiazol-2-yl]-amide；8-[[4-(3-nitrophenyl)-1,3-thiazol-2-yl]amino]-8-oxooctanoic acid
• CAS: 944457-63-0
• 化学式: C₁₇H₁₉N₃O₅S
• 分子量: 377.421
• InChiKey: QRKVCLLXVSMUOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  octanedioic acid [4-(3-nitro-phenyl)thiazol-2-yl]amide 在 三乙胺 、 氯甲酸异丁酯 、 羟胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.42h， 生成 YC-II-90
  参考文献：
  名称：

  Functional Differences in Epigenetic ModulatorsSuperiority of Mercaptoacetamide-Based Histone Deacetylase Inhibitors Relative to Hydroxamates in Cortical Neuron Neuroprotection Studies

  摘要：

  We compare the ability of two structurally different classes of epigenetic modulators, namely, histone deacetylase (HDAC) inhibitors containing either a hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical neurons in culture from oxidative stress-induced death. This study reveals that some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas the hydroxamates show toxicity at higher concentrations. Our present results appear to be consistent with the possibility that the mercaptoacetamide-based HDAC inhibitors interact with a different subset of the HDAC isozymes [less activity at HDAC1 and 2 correlates with less inhibitor toxicity], or alternatively, are interacting selectively with only the cytoplasmic HDACs that are crucial for protection from oxidative stress.

  DOI：

  10.1021/jm070178x
• 作为产物：
  描述：

  octanedioic acid [4-(3-nitro-phenyl)thiazol-2-yl]amide methyl ester 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以85.6%的产率得到octanedioic acid [4-(3-nitro-phenyl)thiazol-2-yl]amide
  参考文献：
  名称：

  WO2008/19025

  摘要：

  公开号：

文献信息

• Isoform Selective HDAC Inhibitors
  申请人：Kozikowski Alan P.

  公开号：US20100196502A1

  公开（公告）日：2010-08-05

  One aspect of the invention relates to isoform-selective HDAC inhibitors. Also provided are methods of sensitizing a cancer cell to the cytotoxic effects of radiotherapy. The invention also provides methods for treating cancer, methods for treating neurological diseases and methods for treating malaria. Additionally, the invention provides pharmaceutical compositions comprising an HDAC inhibitor of the invention; and kits comprising a an HDAC inhibitor of the invention.

  本发明的一个方面涉及选择性同工酶HDAC抑制剂。还提供了一种使癌细胞对放疗的细胞毒性效应敏感的方法。本发明还提供了治疗癌症、神经系统疾病和疟疾的方法。此外，本发明还提供包含本发明的HDAC抑制剂的制药组合物；以及包含本发明的HDAC抑制剂的试剂盒。
• Isoform selective HDAC inhibitors
  申请人：Kozikowski Alan P.

  公开号：US08653278B2

  公开（公告）日：2014-02-18

  One aspect of the invention relates to isoform-selective HDAC inhibitors. Also provided are methods of sensitizing a cancer cell to the cytotoxic effects of radiotherapy. The invention also provides methods for treating cancer, methods for treating neurological diseases and methods for treating malaria. Additionally, the invention provides pharmaceutical compositions comprising an HDAC inhibitor of the invention; and kits comprising an HDAC inhibitor of the invention.

  本发明的一个方面与同工酶选择性 HDAC 抑制剂有关。还提供了一种使癌细胞对放疗的细胞毒性效应敏感的方法。本发明还提供了治疗癌症、神经系统疾病和疟疾的方法。此外，本发明提供了含有本发明的 HDAC 抑制剂的药物组合物；以及包含本发明的 HDAC 抑制剂的试剂盒。
• A Series of Potent and Selective, Triazolylphenyl-Based Histone Deacetylases Inhibitors with Activity against Pancreatic Cancer Cells and <i>Plasmodium falciparum</i>
  作者：Yufeng Chen、Miriam Lopez-Sanchez、Doris N. Savoy、Daniel D. Billadeau、Geoffrey S. Dow、Alan P. Kozikowski

  DOI：10.1021/jm701606b

  日期：2008.6.1

  The discovery of the rules governing the inhibition of the various HDAC isoforms is likely to be key to identifying improved therapeutics that act as epigenetic modulators of gene transcription. Herein we present results on the modification of the CAP region of a set of triazolylphenyl-based HDACIs, and show that the nature of substitution on the phenyl ring plays a role in their selectivity for HDAC1 versus HDAC6, with low to moderate selectivity (2-51-fold) being achieved. In light of the valuable selectivity and potency that were identified for the triazolylphenyl ligand 6b in the inhibition of HDAC6 (IC50 = 1.9 nM), this compound represents a valuable research tool and a candidate for further chemical modifications. Lastly, these new HDACIs were studied for both their anticancer and antimalarial activity, which serve to validate the superior activity of the HDACI 10c.
• US8653278B2
  申请人：——

  公开号：US8653278B2

  公开（公告）日：2014-02-18