(1R,2R)-2-N-(tetradecanoylamino)-1-hydroxy-1-(4'-nitrophenyl)propyl-3-O-(N,N-dimethylamino)acetate

• 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: (1R,2R)-2-N-(tetradecanoylamino)-1-hydroxy-1-(4'-nitrophenyl)propyl-3-O-(N,N-dimethylamino)acetate
• 英文别名: [(2R,3R)-3-hydroxy-3-(4-nitrophenyl)-2-(tetradecanoylamino)propyl] 2-(dimethylamino)acetate
• 化学式: C₂₇H₄₅N₃O₆
• 分子量: 507.671
• InChiKey: VVFUALYVUXJPAN-SHQCIBLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  36
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-N-(tetradecanoylamino)-1-hydroxy-1-(4'-nitrophenyl)propyl-3-O-(N,N-dimethylamino)acetate 在 盐酸 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 生成 (1R,2R)-2-N-(tetradecanoylamino)-1-hydroxy-1-(4'-nitrophenyl)propyl-3-O-(N,N-dimethylamino)acetate hydrochloride
  参考文献：
  名称：

  Targeting (cellular) lysosomal acid ceramidase by B13: Design, synthesis and evaluation of novel DMG-B13 ester prodrugs

  摘要：

  Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. The present study concentrates on the lysosomal targeting of B13 via its N, N-dimethylglycine (DMG) esters (DMG-B13 prodrugs). Novel analogs, the isomeric mono-DMG-B13, LCL522 (3-O-DMG-B13 center dot HCl) and LCL596 (1-O-DMG-B13 center dot HCl) and di-DMG-B13, LCL521 (1,3-O, O-DMGB13 center dot 2HCl) conjugates, were designed and synthesized through N, N-dimethyl glycine (DMG) esterification of the hydroxyl groups of B13. In MCF7 cells, DMG-B13 prodrugs were efficiently metabolized to B13. The early inhibitory effect of DMG-B13 prodrugs on cellular ceramidases was ACDase specific by their lysosomal targeting. The corresponding dramatic decrease of cellular Sph (80-97% Control/1 h) by DMG-B13 prodrugs was mainly from the inhibition of the lysosomal ACDase. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.025
• 作为产物：
  描述：

  (1R,2R)-N-myristoylamino-4'-nitrophenylpropanediol-1,3 、 N,N-二甲基甘氨酸 在 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (1R,2R)-2-N-(tetradecanoylamino)-1-hydroxy-1-(4'-nitrophenyl)propyl-3-O-(N,N-dimethylamino)acetate
  参考文献：
  名称：

  Targeting (cellular) lysosomal acid ceramidase by B13: Design, synthesis and evaluation of novel DMG-B13 ester prodrugs

  摘要：

  Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. The present study concentrates on the lysosomal targeting of B13 via its N, N-dimethylglycine (DMG) esters (DMG-B13 prodrugs). Novel analogs, the isomeric mono-DMG-B13, LCL522 (3-O-DMG-B13 center dot HCl) and LCL596 (1-O-DMG-B13 center dot HCl) and di-DMG-B13, LCL521 (1,3-O, O-DMGB13 center dot 2HCl) conjugates, were designed and synthesized through N, N-dimethyl glycine (DMG) esterification of the hydroxyl groups of B13. In MCF7 cells, DMG-B13 prodrugs were efficiently metabolized to B13. The early inhibitory effect of DMG-B13 prodrugs on cellular ceramidases was ACDase specific by their lysosomal targeting. The corresponding dramatic decrease of cellular Sph (80-97% Control/1 h) by DMG-B13 prodrugs was mainly from the inhibition of the lysosomal ACDase. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.025

文献信息

• Targeting (cellular) lysosomal acid ceramidase by B13: Design, synthesis and evaluation of novel DMG-B13 ester prodrugs
  作者：Aiping Bai、Zdzislaw M. Szulc、Jacek Bielawski、Jason S. Pierce、Barbara Rembiesa、Silva Terzieva、Cungui Mao、Ruijuan Xu、Bill Wu、Christopher J. Clarke、Benjamin Newcomb、Xiang Liu、James Norris、Yusuf A. Hannun、Alicja Bielawska

  DOI：10.1016/j.bmc.2014.10.025

  日期：2014.12

  Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. The present study concentrates on the lysosomal targeting of B13 via its N, N-dimethylglycine (DMG) esters (DMG-B13 prodrugs). Novel analogs, the isomeric mono-DMG-B13, LCL522 (3-O-DMG-B13 center dot HCl) and LCL596 (1-O-DMG-B13 center dot HCl) and di-DMG-B13, LCL521 (1,3-O, O-DMGB13 center dot 2HCl) conjugates, were designed and synthesized through N, N-dimethyl glycine (DMG) esterification of the hydroxyl groups of B13. In MCF7 cells, DMG-B13 prodrugs were efficiently metabolized to B13. The early inhibitory effect of DMG-B13 prodrugs on cellular ceramidases was ACDase specific by their lysosomal targeting. The corresponding dramatic decrease of cellular Sph (80-97% Control/1 h) by DMG-B13 prodrugs was mainly from the inhibition of the lysosomal ACDase. (C) 2014 Elsevier Ltd. All rights reserved.