(S)-2-Acetylamino-6-(2-{2-[3-((R)-2,4-dihydroxy-3,3-dimethyl-butyrylamino)-propionylamino]-ethylsulfanyl}-acetylamino)-hexanoic acid amide | 639513-09-0

• 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-{2-[3-((R)-2,4-dihydroxy-3,3-dimethyl-butyrylamino)-propionylamino]-ethylsulfanyl}-acetylamino)-hexanoic acid amide
• CAS: 639513-09-0
• 化学式: C₂₁H₃₉N₅O₇S
• 分子量: 505.636
• InChiKey: IRAMBNLJDMKCQP-YJBOKZPZSA-N

物化性质

• 沸点：
  1003.4±65.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.0
• 重原子数：
  34.0
• 可旋转键数：
  18.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  199.95
• 氢给体数：
  7.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (S)-2-Acetylamino-6-(2-{2-[3-((R)-2,4-dihydroxy-3,3-dimethyl-butyrylamino)-propionylamino]-ethylsulfanyl}-acetylamino)-hexanoic acid amide 在 四氮唑 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 Phosphoric acid mono-[(R)-3-(2-{2-[((S)-5-acetylamino-5-carbamoyl-pentylcarbamoyl)-methylsulfanyl]-ethylcarbamoyl}-ethylcarbamoyl)-3-hydroxy-2,2-dimethyl-propyl] 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：

  泛硫醇 、 (S)-2-Acetylamino-6-(2-bromo-acetylamino)-hexanoic acid amide 在 盐酸 、 三苯基膦 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.5h， 以460 mg的产率得到(S)-2-Acetylamino-6-(2-{2-[3-((R)-2,4-dihydroxy-3,3-dimethyl-butyrylamino)-propionylamino]-ethylsulfanyl}-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