16-triphenylmethoxy-1-hexadecanol | 745073-18-1

• 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: 16-triphenylmethoxy-1-hexadecanol
• 英文别名: 16-(trityloxy)-1-hexadecanol；16-Trityloxyhexadecan-1-ol
• CAS: 745073-18-1
• 化学式: C₃₅H₄₈O₂
• 分子量: 500.765
• InChiKey: QWHLZJYCQVXHOA-UHFFFAOYSA-N

物化性质

• 沸点：
  593.4±45.0 °C(Predicted)
• 密度：
  0.999±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.9
• 重原子数：
  37
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  16-triphenylmethoxy-1-hexadecanol 在 重铬酸吡啶 、 甲酸 、 ammonium cerium(IV) nitrate 、 pyridinium chloroformate 、 4 A molecular sieve 、 甲基磺酰氯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.0h， 生成 5-(benzyloxy)methyl-3-[(E)-16-carboxypentadecylidene]-5-hydroxymethyltetrahydro-2-furanone
  参考文献：
  名称：

  Macrocyclic Diacylglycerol-bis-lactones as Conformationally Constrained Analogues of Diacylglycerol-lactones. Interactions with Protein Kinase C

  摘要：

  A series of macrocyclic diacylglycerol (DAG)-bis-lactones were investigated as extreme conformationally constrained analogues of DAG-lactones in order to seek more potent protein kinase C (PKC) ligands with higher binding affinities and less lipophilicity than previous compounds. The additional constraint achieved the desired objective as exemplified by the macrocyclic DAG-bis-lactone 57, which exhibited a 6-fold higher binding affinity for PKCalpha (K-i = 6.07 nM) than the corresponding nonmacrocyclic 3-alkylidene DAG-lactone 6. A structure-activity relationship (SAR) analysis of the macrocyclic DAG-bis-lactones demonstrated a parabolic relationship between activity and lipophilicity, as well as a predilection for the Z-alkylidene isomers as the preferred ligands. Molecular docking studies revealed that macrocyclic DAG-bis-lactone 57 bound to the C1b domain of PKCalpha exclusively in the sn-1 binding mode in contrast to DAG-lactone 6, which showed both sn-1 and sn-2 binding modes. It is proposed that the high potency displayed by these macrocyclic DAG-bis-lactones results from a set of more favorable hydrogen bonding and hydrophobic interactions with PKCalpha as well as from a reduced entropy penalty due to conformational restriction.

  DOI：

  10.1021/jm0497747
• 作为产物：
  描述：

  16-羟基棕榈酸 在 lithium aluminium tetrahydride 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 16-triphenylmethoxy-1-hexadecanol
  参考文献：
  名称：

  [EN] ENDOSOMOLYTIC AGENTS FOR GENE THERAPY
  [FR] AGENTS ENDOSOMOLYTIQUES POUR THÉRAPIE GÉNIQUE

  摘要：

  式(I)的化合物，其中Ar是一种芳基，可选择性地进一步取代为一个或多个基团R3；A是一个亲脂性、疏水性的基团；R1是一个磷酸二酯、磷酸三酯、硫醚或酰胺基团；X是一个未取代或取代的C6到C24烷基或烯基基团，该基团可被一个或多个-NR9-、-O-或-S-键所中断；R2是-YC(R4)(R5)CO2R6；以及其药学上可接受的盐或溶剂化合物，可用作内体溶解剂，特别用于传递在基因治疗中有用的核酸。

  公开号：

  WO2018060280A1

文献信息

• Endosomolytic agents for gene therapy
  申请人：UCB Biopharma SRL

  公开号：US10842884B2

  公开（公告）日：2020-11-24

  Compounds of formula (I), wherein Ar is an aryl group optionally further substituted with one or more groups R3; A is a lipophilic, hydrophobic moiety; R1 is a phosphodiester, phosphotriester, thioether or amide group; X is an unsubstituted or substituted C6 to C24 alkylene or alkenylene group, which is optionally interrupted by one or more —NR9—, —O— or —S— linkages, R2 is —YC(R4)(R5)CO2R6; and pharmaceutically acceptable salts or solvates thereof are useful as endosomolytic agents particularly for the delivery of nucleic acids useful in gene therapy.

  式(I)化合物，其中 Ar 是可选被一个或多个基团 R3 进一步取代的芳基；A 是亲脂疏水分子；R1 是膦二酯、膦三酯、硫醚或酰胺基团；X 是未取代或取代的 C6 至 C24 亚烷基或烯基，该亚烷基或烯基任选被一个或多个 -NR9-、-O- 或 -S- 连接打断，R2 是 -YC(R4)(R5)CO2R6；其药学上可接受的盐或溶液可用作内溶酶体剂，特别是用于递送基因治疗中有用的核酸。
• ENDOSOMOLYTIC AGENTS FOR GENE THERAPY
  申请人：UCB Biopharma SRL

  公开号：EP3519423B1

  公开（公告）日：2021-04-07
• Endosomolytic Agents for Gene Therapy
  申请人：UCB Biopharma SPRL

  公开号：US20190298859A1

  公开（公告）日：2019-10-03

  Compounds of formula (I), wherein Ar is an aryl group optionally further substituted with one or more groups R 3 ; A is a lipophilic, hydrophobic moiety; R 1 is a phosphodiester, phosphotriester, thioether or amide group; X is an unsubstituted or substituted C 6 to C 24 alkylene or alkenylene group, which is optionally interrupted by one or more —NR 9 —, —O— or —S— linkages, R 2 is —YC(R 4 )(R 5 )CO 2 R 6 ; and pharmaceutically acceptable salts or solvates thereof are useful as endosomolytic agents particularly for the delivery of nucleic acids useful in gene therapy.
• [EN] ENDOSOMOLYTIC AGENTS FOR GENE THERAPY<br/>[FR] AGENTS ENDOSOMOLYTIQUES POUR THÉRAPIE GÉNIQUE
  申请人：UCB BIOPHARMA SPRL

  公开号：WO2018060280A1

  公开（公告）日：2018-04-05

  Compounds of formula (I), wherein Ar is an aryl group optionally further substituted with one or more groups R3; A is a lipophilic, hydrophobic moiety; R1 is a phosphodiester, phosphotriester, thioether or amide group; X is an unsubstituted or substituted C6 to C24 alkylene or alkenylene group, which is optionally interrupted by one or more -NR9-, -O- or -S- linkages, R2 is -YC(R4)(R5)CO2R6; and pharmaceutically acceptable salts or solvates thereof are useful as endosomolytic agents particularly for the delivery of nucleic acids useful in gene therapy.

  式(I)的化合物，其中Ar是一种芳基，可选择性地进一步取代为一个或多个基团R3；A是一个亲脂性、疏水性的基团；R1是一个磷酸二酯、磷酸三酯、硫醚或酰胺基团；X是一个未取代或取代的C6到C24烷基或烯基基团，该基团可被一个或多个-NR9-、-O-或-S-键所中断；R2是-YC(R4)(R5)CO2R6；以及其药学上可接受的盐或溶剂化合物，可用作内体溶解剂，特别用于传递在基因治疗中有用的核酸。
• Macrocyclic Diacylglycerol-bis-lactones as Conformationally Constrained Analogues of Diacylglycerol-lactones. Interactions with Protein Kinase C
  作者：Ji-Hye Kang、Su Yeon Kim、Jeewoo Lee、Victor E. Marquez、Nancy E. Lewin、Larry V. Pearce、Peter M. Blumberg

  DOI：10.1021/jm0497747

  日期：2004.7.1

  A series of macrocyclic diacylglycerol (DAG)-bis-lactones were investigated as extreme conformationally constrained analogues of DAG-lactones in order to seek more potent protein kinase C (PKC) ligands with higher binding affinities and less lipophilicity than previous compounds. The additional constraint achieved the desired objective as exemplified by the macrocyclic DAG-bis-lactone 57, which exhibited a 6-fold higher binding affinity for PKCalpha (K-i = 6.07 nM) than the corresponding nonmacrocyclic 3-alkylidene DAG-lactone 6. A structure-activity relationship (SAR) analysis of the macrocyclic DAG-bis-lactones demonstrated a parabolic relationship between activity and lipophilicity, as well as a predilection for the Z-alkylidene isomers as the preferred ligands. Molecular docking studies revealed that macrocyclic DAG-bis-lactone 57 bound to the C1b domain of PKCalpha exclusively in the sn-1 binding mode in contrast to DAG-lactone 6, which showed both sn-1 and sn-2 binding modes. It is proposed that the high potency displayed by these macrocyclic DAG-bis-lactones results from a set of more favorable hydrogen bonding and hydrophobic interactions with PKCalpha as well as from a reduced entropy penalty due to conformational restriction.