N-(3-hydroxy-2-octoxypropyl)dodecanamide | 207299-01-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-(3-hydroxy-2-octoxypropyl)dodecanamide
• CAS: 207299-01-2
• 化学式: C₂₃H₄₇NO₃
• 分子量: 385.631
• InChiKey: KDYIFGLMUDHPIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  27
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-hydroxy-2-octoxypropyl)dodecanamide 在 吡啶 作用下， 以 四氢呋喃 、 乙醚 、 氯仿 、 异丙醇 为溶剂， 反应 10.0h， 生成 3-dodecanamido-2-octyloxypropylphosphocholine
  参考文献：
  名称：

  Structure−Activity Relationship for Enhancement of Paracellular Permeability across Caco-2 Cell Monolayers by 3-Alkylamido-2-alkoxypropylphosphocholines

  摘要：

  Paracellular permeability enhancers have been used to improve the oral bioavailability of hydrophilic drugs; however, the mechanism of action of many enhancers is poorly understood. In this study, highly potent enhancers of paracellular permeability were identified in the 3-alkylamido-2-alkoxypropylphosphocholine series, and a structure-activity relationship was developed for enhancement of paracellular permeability across Caco-2 cell monolayers. Compounds with short (<5 carbons) hydrocarbon chains at both C-2 and C-3 were generally inactive. The potency exhibited a parabolic relationship with respect to the chain length at either C-2 or C-3. Linear molecules (i.e., compounds with a short hydrocarbon chain at C-2 or C-3 and a long hydrocarbon chain on C-3 or C-2, respectively) were more potent than the corresponding branched molecules with the same carbon load. The efficacy of 3-alkylamido2-alkoxypropylphosphocholines as enhancers of paracellular permeability was not dependent on their existence in micellar form or their ability to alter the fluidity of cell membrane. Previously, a correlation-between the potency of alkylphosphocholines as enhancers of paracellular permeability and the inhibitors of phospholipase C (PLC) was established in Madine Darby canine kidney (MDCK) cell monolayers. The potencies of selected 3-alkylamido-2-alkoxypropylphosphocholines as inhibitors of PLC and enhancers of paracellular permeability fit well into this correlation. Therefore, phosphocholines are likely to increase paracellular permeability by modulating the signal transduction pathway initiated by a PLC-catalyzed reaction rather than by physically altering the cell membrane.

  DOI：

  10.1021/jm020001x
• 作为产物：
  描述：

  3-lauroylamino-1,2-propanediol 在 吡啶 、 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-(3-hydroxy-2-octoxypropyl)dodecanamide
  参考文献：
  名称：

  Structure—activity relationships for enhancement of paracellular permeability by 2-alkoxy-3-alkylamidopropylphosphocholines across Caco-2 cell monolayers

  摘要：

  The oral route is the preferred route of delivery for a large number of drug molecules. However, the intestinal epithelium presents a formidable barrier for delivery of drugs into systemic circulation. Phospholipids are among compounds that enhance the absorption of drugs across the intestinal epithelium. In this paper, we describe structure-activity relationships for phospholipid derivatives as enhancers of paracellular permeability across Caco-2 cell monolayers. in a series of 2-alkoxy-3-alkylamidopropylphosphocholine derivatives, compounds with a long chain at C-3 (R-3) and short chain at C-2 (R-2) were potent in causing a decrease in transepithelial electrical resistance (TEER) and an increase in mannitol transport, but also showed significant cytotoxicity. Compounds with 9-11 carbons at C-3 and 6-10 carbons at C-2 provided good separation (up to 2.7-fold) between activity and cytotoxicity. Notably, a good correlation (r(2) = 0.93) was observed between EC50 (TEER) [concentration that caused a drop in TEER to 50% of its control (untreated) value] and EC10X (mannitol) [concentration that caused 10-fold increase in mannitol transport over the control (untreated) value], confirming that a decrease in TEER is associated with enhanced permeability of the hydrophilic compounds across Caco-2 cell monolayers. Compounds with medium to long carbon chains at C-2 and C-3, and the total carbons in the alkyl chains > 20, showed poor activity and no cytotoxicity.

  DOI：

  10.1021/js9900957

文献信息

• Compositions and methods of double-targeting virus infections and cancer cells
  申请人：——

  公开号：US20020082242A1

  公开（公告）日：2002-06-27

  The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds, which comprise a phosphocholine moiety covalently conjugated with one or more therapeutic agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and facilitating delivery of a therapeutic agent to a mammalian cell. The compositions of the invention include compounds, which comprise an alkyl lipid or phospholipid moiety covalently conjugated with a therapeutic agent (e.g., a nucleoside analogue). The invention also includes pharmaceutical compositions for combating cancer and facilitating delivery of a therapeutic agent to a mammalian cell. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt or a prodrug thereof, or a pharmaceutical composition of the invention, in an amount effective to combat a cancer or to facilitate delivery of a therapeutic agent to a mammalian cell.

  本发明涉及的组合物和方法可用于治疗哺乳动物病毒感染，通过双重靶向病毒（即在病毒生命周期的多个阶段靶向病毒），从而抑制病毒复制。本发明的组合物包括化合物，该化合物包括与一个或多个治疗剂（例如核苷类似物、蛋白酶抑制剂等）共价结合到脂质骨架上的磷酸胆碱基团。本发明还包括用于治疗哺乳动物病毒感染的制药组合物。本发明的方法包括向感染病毒的哺乳动物注射本发明的化合物、药学上可接受的盐或其前药，或本发明的制药组合物，以有效治疗感染。此外，本发明还包括用于对抗哺乳动物癌症和促进递送治疗剂到哺乳动物细胞的组合物和方法。本发明的组合物包括与治疗剂（例如核苷类似物）共价结合的烷基脂质或磷脂酰胆碱基团。本发明还包括用于对抗癌症和促进递送治疗剂到哺乳动物细胞的制药组合物。本发明的方法包括向哺乳动物注射本发明的化合物、药学上可接受的盐或其前药，或本发明的制药组合物，以有效对抗癌症或促进递送治疗剂到哺乳动物细胞。
• Compositions and methods for targeting cancer cells
  申请人：University of North Carolina at Chapel Hill

  公开号：US20040161398A1

  公开（公告）日：2004-08-19

  The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell. The compositions of the invention include compounds which comprise an alkyl lipid or phospholipid moiety covalently conjugated with an anticancer agent (e.g. a nucleoside analogue). The invention also includes pharmaceutical compositions and kits for combating a cancer and for facilitating delivery of a therapeutic agent to a mammalian cell. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to combat a cancer or to facilitate delivery of a therapeutic agent to a mammalian cell.

  本发明包括用于哺乳动物病毒感染治疗的组合物和方法，通过双重靶向病毒（即在病毒生命周期的多个阶段靶向病毒），从而抑制病毒复制。本发明的组合物包括将磷酸胆碱基团与一个或多个抗病毒剂（例如核苷类似物，蛋白酶抑制剂等）共价结合到脂质骨架上的化合物。本发明还包括用于哺乳动物病毒感染治疗的制药组合物和工具包。本发明的方法包括向感染病毒的哺乳动物投与本发明的化合物、其药学可接受的盐或本发明的制药组合物，以有效治疗感染。此外，本发明还包括用于对抗哺乳动物癌症和促进递送治疗剂到哺乳动物细胞的组合物和方法。本发明的组合物包括将烷基脂质或磷脂基团与抗癌剂（例如核苷类似物）共价结合的化合物。本发明还包括用于对抗癌症和促进递送治疗剂到哺乳动物细胞的制药组合物和工具包。本发明的方法包括向哺乳动物投与本发明的化合物、其药学可接受的盐或本发明的制药组合物，以有效对抗癌症或促进递送治疗剂到哺乳动物细胞。
• Compositions and Methods for Double-Targeting Virus Infections and Targeting Cancer Cells
  申请人：KUCERA Louis S.

  公开号：US20100184718A1

  公开（公告）日：2010-07-22

  The invention includes compositions and methods useful for treatment of a virus infection in a mammal by double-targeting the virus (i.e. targeting the virus at more than one stage of the virus life cycle) and thereby inhibiting virus replication. The compositions of the invention include compounds which comprise a phosphocholine moiety covalently conjugated with one or more antiviral agents (e.g. nucleoside analogue, protease inhibitor, etc.) to a lipid backbone. The invention also includes pharmaceutical compositions and kits for use in treatment of a virus infection in mammals. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to treat the infection, to a mammal infected with a virus. Additionally, the invention includes compositions and methods useful for combating a cancer in a mammal and for facilitating delivery of a therapeutic agent to a mammalian cell. The compositions of the invention include compounds which comprise an alkyl lipid or phospholipid moiety covalently conjugated with an anticancer agent (e.g. a nucleoside analogue). The invention also includes pharmaceutical compositions and kits for combating a cancer and for facilitating delivery of a therapeutic agent to a mammalian cell. The methods of the invention comprise administering a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the invention, in an amount effective to combat a cancer or to facilitate delivery of a therapeutic agent to a mammalian cell.

  本发明涉及一种用于哺乳动物病毒感染治疗的组合物和方法，通过双重靶向病毒（即在病毒生命周期的多个阶段靶向病毒），从而抑制病毒复制。本发明的组合物包括将磷酸胆碱基团共价结合到一个或多个抗病毒剂（如核苷类似物，蛋白酶抑制剂等）与脂质骨架上的化合物。本发明还包括用于哺乳动物病毒感染治疗的药物组合物和工具包。本发明的方法包括向感染病毒的哺乳动物中投与本发明的化合物、其药学上可接受的盐或本发明的药物组合物，以有效治疗感染。此外，本发明还包括用于对抗哺乳动物癌症和促进将治疗剂递送到哺乳动物细胞的组合物和方法。本发明的组合物包括将烷基脂或磷脂基团共价结合到抗癌剂（如核苷类似物）上的化合物。本发明还包括用于对抗癌症和促进将治疗剂递送到哺乳动物细胞的药物组合物和工具包。本发明的方法包括向哺乳动物中投与本发明的化合物、其药学上可接受的盐或本发明的药物组合物，以有效对抗癌症或促进将治疗剂递送到哺乳动物细胞。
• Structure—activity relationships for enhancement of paracellular permeability by 2-alkoxy-3-alkylamidopropylphosphocholines across Caco-2 cell monolayers
  作者：Dong-Zhou Liu、Susan L. Morris-Natschke、Louis S. Kucera、Khalid S. Ishaq、Dhiren R. Thakker

  DOI：10.1021/js9900957

  日期：1999.11

  The oral route is the preferred route of delivery for a large number of drug molecules. However, the intestinal epithelium presents a formidable barrier for delivery of drugs into systemic circulation. Phospholipids are among compounds that enhance the absorption of drugs across the intestinal epithelium. In this paper, we describe structure-activity relationships for phospholipid derivatives as enhancers of paracellular permeability across Caco-2 cell monolayers. in a series of 2-alkoxy-3-alkylamidopropylphosphocholine derivatives, compounds with a long chain at C-3 (R-3) and short chain at C-2 (R-2) were potent in causing a decrease in transepithelial electrical resistance (TEER) and an increase in mannitol transport, but also showed significant cytotoxicity. Compounds with 9-11 carbons at C-3 and 6-10 carbons at C-2 provided good separation (up to 2.7-fold) between activity and cytotoxicity. Notably, a good correlation (r(2) = 0.93) was observed between EC50 (TEER) [concentration that caused a drop in TEER to 50% of its control (untreated) value] and EC10X (mannitol) [concentration that caused 10-fold increase in mannitol transport over the control (untreated) value], confirming that a decrease in TEER is associated with enhanced permeability of the hydrophilic compounds across Caco-2 cell monolayers. Compounds with medium to long carbon chains at C-2 and C-3, and the total carbons in the alkyl chains > 20, showed poor activity and no cytotoxicity.
• COMPOSITIONS AND METHODS FOR DOUBLE-TARGETING VIRUS INFECTIONS AND TARGETING CANCER CELLS
  申请人：WAKE FOREST UNIVERSITY

  公开号：EP1228080A2

  公开（公告）日：2002-08-07