[(2R)-2-(3-carboxypropanoyloxy)-4-oxo-4-phenylmethoxybutyl]-trimethylazanium | 952564-16-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(2R)-2-(3-carboxypropanoyloxy)-4-oxo-4-phenylmethoxybutyl]-trimethylazanium
• CAS: 952564-16-8
• 化学式: C₁₈H₂₆NO₆
• 分子量: 352.408
• InChiKey: YXSWTRODMVNMED-OAHLLOKOSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(2R)-2-(3-carboxypropanoyloxy)-4-oxo-4-phenylmethoxybutyl]-trimethylazanium 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Combination of l-Carnitine with Lipophilic Linkage-Donating Gemcitabine Derivatives as Intestinal Novel Organic Cation Transporter 2-Targeting Oral Prodrugs

  摘要：

  Novel organic cation transporter 2 (OCTN2, SLC22A5) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of L-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2.

  DOI：

  10.1021/acs.jmedchem.7b00049
• 作为产物：
  描述：

  左旋肉碱 在 N,N-二甲基甲酰胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 [(2R)-2-(3-carboxypropanoyloxy)-4-oxo-4-phenylmethoxybutyl]-trimethylazanium
  参考文献：
  名称：

  Combination of l-Carnitine with Lipophilic Linkage-Donating Gemcitabine Derivatives as Intestinal Novel Organic Cation Transporter 2-Targeting Oral Prodrugs

  摘要：

  Novel organic cation transporter 2 (OCTN2, SLC22A5) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of L-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2.

  DOI：

  10.1021/acs.jmedchem.7b00049

文献信息

• 一类L-肉毒碱两亲性衍生物及其修饰的纳米 粒及其用途
  申请人：沈阳药科大学

  公开号：CN107519496B

  公开（公告）日：2019-12-10

  本发明属于药物制剂新辅料和新剂型领域，涉及一类L‑肉毒碱两亲性衍生物及其修饰的纳米粒。还涉及L‑肉毒碱衍生物及其修饰的纳米粒的制备，及其L‑肉毒碱衍生物作为药物递送载体在脑部药物递送方面的应用。本发明利用血脑屏障和脑胶质瘤表面高表达的OCTN2转运体作为靶点，合成L‑肉毒碱两亲性衍生物，采用物理镶嵌的方法修饰纳米粒使其表面携带L‑肉毒碱，以生物相容性好的高分子材料为基础载体，包载抗肿瘤药物后制成基于OCTN2转运体的脑胶质瘤靶向药物递送系统，用于提高纳米载体的脑内分布及脑胶质瘤治疗效果。所述的两亲性化合物结构如下：
• Carnitine Conjugates of Adamantanamines and Neramexane Derivatives as Dual Prodrugs for Various Uses
  申请人：Goel Om P.

  公开号：US20090246267A1

  公开（公告）日：2009-10-01

  This invention concerns compounds of adamantanamines and neramexane, including their pharmaceutically-acceptable salts, diesterioisomers, and formulations for treating Alzheimer's related dementias, depression, AIDS related dementias, as antivirals, inflammatory diseases such as rheumatoid arthritis, and cerebral ischemia, hyperlipidemia, and diabetes.
• CARNITINE CONJUGATES OF ADAMANTANAMINES DERIVATIVES AS DUAL PRODRUGS FOR VARIOUS USES
  申请人：Goel Om P.

  公开号：US20110212166A1

  公开（公告）日：2011-09-01

  This invention concerns compounds of adamantanamines and neramexane, including their pharmaceutically-acceptable salts, diesterioisomers, and formulations for treating Alzheimer's related dementias, depression, AIDS related dementias, as antivirals, inflammatory diseases such as rheumatoid arthritis, and cerebral ischemia, hyperlipidemia, and diabetes.
• US7977511B2
  申请人：——

  公开号：US7977511B2

  公开（公告）日：2011-07-12
• US8049038B2
  申请人：——

  公开号：US8049038B2

  公开（公告）日：2011-11-01