N-(2-hydroxy-3-trityloxypropyl)dodecanamide | 207299-00-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-(2-hydroxy-3-trityloxypropyl)dodecanamide
• CAS: 207299-00-1
• 化学式: C₃₄H₄₅NO₃
• 分子量: 515.736
• InChiKey: OBIMKAZGAANWJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  38
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 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-(2-hydroxy-3-trityloxypropyl)dodecanamide 在 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 3-[[3-(Dodecanoylamino)-2-octoxy-propoxy]-hydroxy-phosphoryl]oxypropyl-trimethyl-ammonium
  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
• 作为产物：
  描述：

  月桂酰氯 生成 N-(2-hydroxy-3-trityloxypropyl)dodecanamide
  参考文献：
  名称：

  Methods and compositions for the treatment of respiratory syncytial virus

  摘要：

  该发明包括用于抑制RSV复制和治疗感染RSV的宿主的化合物。该发明还包括通过向宿主施用该发明的化合物的抗RSV有效量来治疗感染RSV的宿主的方法。

  公开号：

  US20050187191A1

文献信息

• Methods and compositions for the treatment of respiratory syncytial virus
  申请人：Kucera S. Louis

  公开号：US20050187191A1

  公开（公告）日：2005-08-25

  The invention includes compounds useful for inhibiting RSV replication and treating a host infected with RSV. The invention also includes methods of treating a host infected with RSV by administering to the host an anti-RSV effective amount of a compound of the invention.

  该发明包括用于抑制RSV复制和治疗感染RSV的宿主的化合物。该发明还包括通过向宿主施用该发明的化合物的抗RSV有效量来治疗感染RSV的宿主的方法。
• Structure−Activity Relationship for Enhancement of Paracellular Permeability across Caco-2 Cell Monolayers by 3-Alkylamido-2-alkoxypropylphosphocholines
  作者：Hui Ouyang、Susan L. Morris-Natschke、Khalid S. Ishaq、Peter Ward、Dongzhou Liu、Sarah Leonard、Dhiren R. Thakker

  DOI：10.1021/jm020001x

  日期：2002.6.1

  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.
• 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.