(1R,2R)-2-N-(tetradecanoylamino)-1-hydroxy-1-(4'-nitrophenyl)propyl-3-O-(N,N-dimethylamino)acetate hydrochloride | 1226759-49-4

• 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 hydrochloride
• 英文别名: LCL522；(1R,2R)-2-[N-tetradecanoyl-amino]-1-(4"-nitrophenyl)-1,3-propandiol-1-O-dimethylglycine hydrochloride；[(2R,3R)-3-hydroxy-3-(4-nitrophenyl)-2-(tetradecanoylamino)propyl] 2-(dimethylamino)acetate;hydrochloride
• CAS: 1226759-49-4
• 化学式: C₂₇H₄₅N₃O₆*ClH
• 分子量: 544.132
• InChiKey: AVKXYXAMSXRKDL-ITTCRWFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.34
• 重原子数：
  37
• 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：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  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

文献信息

• [EN] LYSOSOMOTROPIC INHIBITORS OF ACID CERAMIDASE<br/>[FR] INHIBITEURS LYSOSOMOTROPES DE CÉRAMIDASE ACIDE
  申请人：MUSC FOUND FOR RES DEV

  公开号：WO2010054223A1

  公开（公告）日：2010-05-14

  The presently disclosed subject matter provides compounds of the formula, formula (Ia): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, and n are as defined herein. Also disclosed are methods for making the compounds of the formula as set forth hereinabove, their use in inhibiting acid ceramidase and ceramidase-related activity, and their use as drugs and prodrugs in the treatment and/or prevention of diseases associated with undesirable ceramidase or sphingosine kinase activity, including, but not limited to, cancer, cancer metastasis, atherosclerosis, stenosis, inflammation, asthma, and atopic dermatitis.

  目前公开的主题提供了以下公式化合物，公式（Ia）：及其药用可接受的盐，其中R1、R2、R3、R4、R5、X、Y和n的定义如本文所述。还公开了制备上述公式化合物的方法，以及它们在抑制酸酶和与酶相关的活性中的应用，以及它们作为药物和前药在治疗和/或预防与不良酶或鞘氨醇激酶活性相关的疾病中的用途，包括但不限于癌症、癌症转移、动脉粥样硬化、狭窄、炎症、哮喘和特应性皮炎。