(S)-2-Acetylamino-6-(2-bromo-acetylamino)-hexanoic acid amide | 639513-13-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-Acetylamino-6-(2-bromo-acetylamino)-hexanoic acid amide
• CAS: 639513-13-6
• 化学式: C₁₀H₁₈BrN₃O₃
• 分子量: 308.175
• InChiKey: MCEBVHOHLAOCAA-QMMMGPOBSA-N

物化性质

• 沸点：
  643.5±55.0 °C(Predicted)
• 密度：
  1.401±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.34
• 重原子数：
  17.0
• 可旋转键数：
  8.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  101.29
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-2-Acetylamino-6-(2-bromo-acetylamino)-hexanoic acid amide 在 四氮唑 、 盐酸 、 三苯基膦 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 Phosphoric acid (R)-3-(2-{2-[((S)-5-acetylamino-5-carbamoyl-pentylcarbamoyl)-methylsulfanyl]-ethylcarbamoyl}-ethylcarbamoyl)-3-hydroxy-2,2-dimethyl-propyl ester dibenzyl ester
  参考文献：
  名称：

  Synthesis and analysis of potential prodrugs of coenzyme A analogues for the inhibition of the histone acetyltransferase p300

  摘要：

  Lys-CoA (1) is a selective inhibitor of p300 histone acetyltransferase (HAT) but shows poor pharmacokinetic properties because of its multiply charged phosphates. In an effort to overcome this limitation, truncated derivatives of I were designed, synthesized and tested as p300HAT inhibitors as well as substrates for the CoA biosynthetic bifunctional enzyme phosphopantetheine adenylyltransferase-dephospho-CoA kinase (PPAT/DPCK). Lys-pantetheine (3) and Lys-phosphopantetheine (2) showed no detectable p300HAT inhibition whereas 3-dephospho-Lys-CoA (5) was a modest p300 inhibitor with IC50 of 1.6 muM (compared to IC50 of similar to50 nM for 1 blocking p300). Compound 2 was shown to be an efficient substrate for PPAT whereas 5 was a very poor DPCK substrate. Further analysis with 3'-dephospho-Me-SCoA (7) indicated that DPCK shows relatively narrow capacity to accept substrates with sulfur substitution. While these results suggest that truncated derivatives of 1 will be of limited value as lead agents for p300 blockade in vivo, they augur well for prodrug versions of CoA analogues that do not require 3'-phosphate substitution for efficient binding to their targets, such as the GCN-5 related N-acetyltransferases. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00265-7
• 作为产物：
  描述：

  乙酸酐 、 溴乙酸 、 Fmoc-Lys(Dde)-OH 以300 mg的产率得到(S)-2-Acetylamino-6-(2-bromo-acetylamino)-hexanoic acid amide
  参考文献：
  名称：

  Synthesis and analysis of potential prodrugs of coenzyme A analogues for the inhibition of the histone acetyltransferase p300

  摘要：

  Lys-CoA (1) is a selective inhibitor of p300 histone acetyltransferase (HAT) but shows poor pharmacokinetic properties because of its multiply charged phosphates. In an effort to overcome this limitation, truncated derivatives of I were designed, synthesized and tested as p300HAT inhibitors as well as substrates for the CoA biosynthetic bifunctional enzyme phosphopantetheine adenylyltransferase-dephospho-CoA kinase (PPAT/DPCK). Lys-pantetheine (3) and Lys-phosphopantetheine (2) showed no detectable p300HAT inhibition whereas 3-dephospho-Lys-CoA (5) was a modest p300 inhibitor with IC50 of 1.6 muM (compared to IC50 of similar to50 nM for 1 blocking p300). Compound 2 was shown to be an efficient substrate for PPAT whereas 5 was a very poor DPCK substrate. Further analysis with 3'-dephospho-Me-SCoA (7) indicated that DPCK shows relatively narrow capacity to accept substrates with sulfur substitution. While these results suggest that truncated derivatives of 1 will be of limited value as lead agents for p300 blockade in vivo, they augur well for prodrug versions of CoA analogues that do not require 3'-phosphate substitution for efficient binding to their targets, such as the GCN-5 related N-acetyltransferases. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00265-7

文献信息

• Bisubstrate Inhibitors of the MYST HATs Esa1 and Tip60
  作者：Jiang Wu、Nan Xie、Zhikun Wu、Ying Zhang、Yujun George Zheng

  DOI：10.1016/j.bmc.2008.12.014

  日期：2009.2

  Esa1 (essential Sas2-related acetyltransferase 1) and Tip60 (HIV-1 TAT-interactive protein, 60 kDa) are key members of the MYST family of histone acetyltransferases (HATs) and play important functions in many cellular processes. In this work, we designed, synthesized and evaluated a series of substrate-based analogs for the inhibition of Esa1 and Tip60. The structures of these analogs feature that

  Esa1（与Sas2相关的必不可少的乙酰基转移酶1）和Tip60（HIV-1 TAT相互作用蛋白，60 kDa）是MYST组蛋白乙酰基转移酶（HATs）的关键成员，在许多细胞过程中起重要作用。在这项工作中，我们设计，合成和评估了一系列基于底物的类似物，可抑制Esa1和Tip60。这些类似物的结构特征在于辅酶A与组蛋白肽底物中乙酰基赖氨酸残基的侧链氨基共价连接。与小分子姜黄素和熊果酸相比，这些双底物类似物对Esa1和Tip60的抑制作用更强。特别是，H4K16CoA被测试为Esa1和Tip60的最有效抑制剂之一。