N-(2,3-dihydroxypropyl)decanamide | 805252-00-0

• 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-(2,3-dihydroxypropyl)decanamide
• 英文别名: Decanoic acid (2,3-dihydroxy-propyl)-amide
• CAS: 805252-00-0
• 化学式: C₁₃H₂₇NO₃
• mdl: MFCD23199074
• 分子量: 245.362
• InChiKey: LVGUMBSMIUWQFD-UHFFFAOYSA-N

物化性质

• 沸点：
  462.4±35.0 °C(Predicted)
• 密度：
  1.003±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.923
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2,3-dihydroxypropyl)decanamide 在 吡啶 、 甲醇 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 氯仿 、 异丙醇 为溶剂， 反应 33.0h， 生成 2-[[3-(Decanoylamino)-2-hexoxy-propoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-ammonium
  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-氨基-1,2-丙二醇 、 癸酰氯 生成 N-(2,3-dihydroxypropyl)decanamide
  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

• One‐Step Biocatalytic Synthesis of Sustainable Surfactants by Selective Amide Bond Formation**
  作者：Max Lubberink、William Finnigan、Christian Schnepel、Christopher R. Baldwin、Nicholas J. Turner、Sabine L. Flitsch

  DOI：10.1002/anie.202205054

  日期：2022.7.25

  route to commercially important surfactants is presented. A truncated construct of carboxylic acid reductase (CARmm-A) catalyzes amide bond formation between fatty acids and amino alcohols with no esterification observed. The wide substrate scope of the enzyme, co-factor recycling, reaction engineering and up-scaling show the feasibility of this method for synthesis.

  提出了一种获得商业上重要的表面活性剂的酶促途径。截短的羧酸还原酶构建体 (CAR mm -A) 催化脂肪酸和氨基醇之间形成酰胺键，未观察到酯化反应。该酶的广泛底物范围、辅因子回收、反应工程和放大显示了该合成方法的可行性。
• 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.
• US7344868B2
  申请人：——

  公开号：US7344868B2

  公开（公告）日：2008-03-18
• 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.