Phosphoric acid (R)-3-(2-{2-[((S)-5-acetylamino-5-carbamoyl-pentylcarbamoyl)-methylsulfanyl]-ethylcarbamoyl}-ethylcarbamoyl)-3-hydroxy-2,2-dimethyl-propyl ester dibenzyl ester | 639513-14-7

• 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: Phosphoric acid (R)-3-(2-{2-[((S)-5-acetylamino-5-carbamoyl-pentylcarbamoyl)-methylsulfanyl]-ethylcarbamoyl}-ethylcarbamoyl)-3-hydroxy-2,2-dimethyl-propyl ester dibenzyl ester
• CAS: 639513-14-7
• 化学式: C₃₅H₅₂N₅O₁₀PS
• 分子量: 765.865
• InChiKey: NJJRAANRMLJZSI-NYDCQLBNSA-N

物化性质

• 沸点：
  1096.7±65.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  52.0
• 可旋转键数：
  26.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  224.48
• 氢给体数：
  6.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  Phosphoric acid (R)-3-(2-{2-[((S)-5-acetylamino-5-carbamoyl-pentylcarbamoyl)-methylsulfanyl]-ethylcarbamoyl}-ethylcarbamoyl)-3-hydroxy-2,2-dimethyl-propyl ester dibenzyl ester 在 三氟乙酸 作用下， 反应 3.0h， 以54 mg的产率得到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：

  (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