N-(5-amino-pentyl)-2-tritylsulfanyl acetamide | 828920-19-0

• 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: N-(5-amino-pentyl)-2-tritylsulfanyl acetamide
• 英文别名: N-(5-Aminopentyl)-2-[(triphenylmethyl)sulfanyl]acetamide；N-(5-aminopentyl)-2-tritylsulfanylacetamide
• CAS: 828920-19-0
• 化学式: C₂₆H₃₀N₂OS
• 分子量: 418.603
• InChiKey: ZRBOCEWCBRNOJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(5-amino-pentyl)-2-tritylsulfanyl acetamide 在 三乙基硅烷 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 生成 BC-4-55
  参考文献：
  名称：

  Chemistry and biology of mercaptoacetamides as novel histone deacetylase inhibitors

  摘要：

  A series of mercaptoacetamides were designed and synthesized as novel histone deacetylase inhibitors with the aid of modeling. Their ability to inhibit HDAC activity and their effects on cancer cell growth were investigated. Some compounds exhibit better HDAC inhibitory activity than SAHA. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.006
• 作为产物：
  描述：

  三苯基甲醇 在 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 5.0h， 生成 N-(5-amino-pentyl)-2-tritylsulfanyl acetamide
  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

文献信息

• Synthesis and structure‐activity relationship of thiol‐based histone deacetylase 6 inhibitors
  作者：Zheng Guo、Yi Zhang、Ya Bao、Ziyi Huang、Xiu Gu、Guan Wang、Jianqi Li

  DOI：10.1111/cbdd.14055

  日期：2022.7

  ZBG and discussed their structure-activity relationship based on molecular docking. In particular, compound 21, obtained by constantly step-by-step simplification and evolution based on Ricolinostat, a specific HDAC6 inhibitor in Phase II, unexpectedly showed high selectivity (29-fold) and moderate potency (73 nM). Utilizing pyrimidine as a linker in thiol-based HDAC6 inhibitors produces an utterly novel

  选择性组蛋白去乙酰化酶 6 (HDAC6) 抑制剂安全且耐受性良好，脱靶效应较小。然而，大多数可用的 HDAC6 抑制剂含有异羟肟酸盐作为锌结合基团 (ZBG)，其不利的药代动力学特性以及潜在的遗传毒性限制了其在多种疾病中的广泛应用。因此，我们设计并合成了一系列以硫醇为ZBG的选择性HDAC6抑制剂，并基于分子对接讨论了它们的构效关系。特别是化合物21，通过基于 Ricolinostat（一种处于 II 期的特异性 HDAC6 抑制剂）不断逐步简化和进化获得的，出乎意料地显示出高选择性（29 倍）和中等效力（73 nM）。在基于硫醇的 HDAC6 抑制剂中使用嘧啶作为接头会产生一种全新的结构，该结构可能显示出不同的药代动力学特性和遗传毒性。
• Chemistry and biology of mercaptoacetamides as novel histone deacetylase inhibitors
  作者：Bin Chen、Pavel A. Petukhov、Mira Jung、Alfredo Velena、Elena Eliseeva、Anatoly Dritschilo、Alan P. Kozikowski

  DOI：10.1016/j.bmcl.2005.01.006

  日期：2005.3

  A series of mercaptoacetamides were designed and synthesized as novel histone deacetylase inhibitors with the aid of modeling. Their ability to inhibit HDAC activity and their effects on cancer cell growth were investigated. Some compounds exhibit better HDAC inhibitory activity than SAHA. (c) 2005 Elsevier Ltd. All rights reserved.
• 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.
• Functional Differences in Epigenetic ModulatorsSuperiority of Mercaptoacetamide-Based Histone Deacetylase Inhibitors Relative to Hydroxamates in Cortical Neuron Neuroprotection Studies
  作者：Alan P. Kozikowski、Yufeng Chen、Arsen Gaysin、Bin Chen、Melissa A. D'Annibale、Carla M. Suto、Brett C. Langley

  DOI：10.1021/jm070178x

  日期：2007.6.1

  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.