rac-1-O-tetradecyl-3-O-(tert-butyldimethylsilyl)glycerol | 175459-07-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 英文名称: rac-1-O-tetradecyl-3-O-(tert-butyldimethylsilyl)glycerol
• 英文别名: 1-[tert-butyl(dimethyl)silyl]oxy-3-tetradecoxypropan-2-ol
• CAS: 175459-07-1
• 化学式: C₂₃H₅₀O₃Si
• 分子量: 402.734
• InChiKey: JWIQLGCYMKCSFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.09
• 重原子数：
  27
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-1-O-tetradecyl-3-O-(tert-butyldimethylsilyl)glycerol 在 四氢呋喃 、 吡啶 、 四丁基氟化铵 、 水 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 97.0h， 生成 rac-1-O-tetradecyl-2-O-palmitoyl-1-thioglycerol 3-phosphate
  参考文献：
  名称：

  Nucleoside Conjugates. 14. Synthesis and Antitumor Activity of 1-.beta.-D-Arabinofuranosylcytosine Conjugates of Ether Lipids with Improved Water Solubility

  摘要：

  A series of ara-CDP-rac-1-O-alkyl-2-O-acylglycerol (9a-f), analogues of highly active ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (1) and Cytoros(2) (2), was prepared, and solubility, lipophilicity, and structure-activity relationships of these conjugates were investigated. Conjugates 9a-f containing sn-1 alkyl (C-16) and the sn-2 fatty acyl (>C-16) such as conjugate 1 were sparingly soluble. Conjugates 9a-c,e were almost completely solubilized in water by shaking. However, a large portion of conjugates 9d and 9f in water by shaking exist in micelles with mean diameters ranging 7.0-55.2 nm. The partition coefficients (1-octanol/PBS) of the water-soluble conjugates were about 9-18 times greater than that of ara-C. A single dose (300 mg/kg) of conjugates 9d and 9f produced a significant increase in life span (ILS 206 to >543%) with 17-67% long-term survivors (>45 days) in mice bearing ip-implanted L1210 lymphoid leukemia. These results were comparable to those of the previous conjugate 1 and Cytoros (2). In contrast, conjugates 9a-c,e at single doses were less effective (ILS 69-178% with no long-term survivors). However, two (qd, 1, 7) or three (qd 1, 5, 9) divided doses of these conjugates were found to be as effective as a single dose of the previous conjugates. The three divided doses (150 mg/kg per day) of conjugates 9d, 9e, and 9f produced a remarkable antitumor activity in L1210 leukemic mice (ILS >350% with >50% long-term survivors). Because of the convenient formulation and the significant antitumor activities, the water-soluble conjugates 9d, 9e, and 9f warrant further investigation.

  DOI：

  10.1021/jm00010a006
• 作为产物：
  描述：

  溴代十四烷 在 咪唑 、 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 生成 rac-1-O-tetradecyl-3-O-(tert-butyldimethylsilyl)glycerol
  参考文献：
  名称：

  Nucleoside Conjugates. 14. Synthesis and Antitumor Activity of 1-.beta.-D-Arabinofuranosylcytosine Conjugates of Ether Lipids with Improved Water Solubility

  摘要：

  A series of ara-CDP-rac-1-O-alkyl-2-O-acylglycerol (9a-f), analogues of highly active ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (1) and Cytoros(2) (2), was prepared, and solubility, lipophilicity, and structure-activity relationships of these conjugates were investigated. Conjugates 9a-f containing sn-1 alkyl (C-16) and the sn-2 fatty acyl (>C-16) such as conjugate 1 were sparingly soluble. Conjugates 9a-c,e were almost completely solubilized in water by shaking. However, a large portion of conjugates 9d and 9f in water by shaking exist in micelles with mean diameters ranging 7.0-55.2 nm. The partition coefficients (1-octanol/PBS) of the water-soluble conjugates were about 9-18 times greater than that of ara-C. A single dose (300 mg/kg) of conjugates 9d and 9f produced a significant increase in life span (ILS 206 to >543%) with 17-67% long-term survivors (>45 days) in mice bearing ip-implanted L1210 lymphoid leukemia. These results were comparable to those of the previous conjugate 1 and Cytoros (2). In contrast, conjugates 9a-c,e at single doses were less effective (ILS 69-178% with no long-term survivors). However, two (qd, 1, 7) or three (qd 1, 5, 9) divided doses of these conjugates were found to be as effective as a single dose of the previous conjugates. The three divided doses (150 mg/kg per day) of conjugates 9d, 9e, and 9f produced a remarkable antitumor activity in L1210 leukemic mice (ILS >350% with >50% long-term survivors). Because of the convenient formulation and the significant antitumor activities, the water-soluble conjugates 9d, 9e, and 9f warrant further investigation.

  DOI：

  10.1021/jm00010a006

文献信息

• Nucleoside 5'-diphosphate conjugates of ether lipids
  申请人：Health Research, Inc.

  公开号：US05484911A1

  公开（公告）日：1996-01-16

  A compound which exhibits antiviral activity having the formula: ##STR1## wherein; R.sub.1 is selected from the group consisting of alkyls and alkenyls containing from 8 to 22 carbon atoms; A is selected from the group consisting of O and S atoms; R.sub.2 is selected from the group consisting of alkyls and alkenyls containing from 8 to 22 carbon atoms; and the Nucleoside is selected from the group consisting of 2',3'-dideoxynucleosides, 3'-azido-2',3'-dideoxynucleosides, and 2',3'-didehydro-2',3'-dideoxynucleosides.

  具有抗病毒活性的化合物的化学式为：##STR1## 其中; R.sub.1选自含有8至22个碳原子的烷基和烯基组成的群体; A选自O和S原子组成的群体; R.sub.2选自含有8至22个碳原子的烷基和烯基组成的群体; 核苷酸选自2'，3'-二脱氧核苷酸，3'-氮杂基-2'，3'-二脱氧核苷酸和2'，3'-二脱氢-2'，3'-二脱氧核苷酸。
• Nucleoside Conjugates. 14. Synthesis and Antitumor Activity of 1-.beta.-D-Arabinofuranosylcytosine Conjugates of Ether Lipids with Improved Water Solubility
  作者：Chung Hong、Alexander Nechaev、Alan J. Kirisits、Rakesh Vig、Sek-Wen Hui、Charles R. West

  DOI：10.1021/jm00010a006

  日期：1995.5

  A series of ara-CDP-rac-1-O-alkyl-2-O-acylglycerol (9a-f), analogues of highly active ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (1) and Cytoros(2) (2), was prepared, and solubility, lipophilicity, and structure-activity relationships of these conjugates were investigated. Conjugates 9a-f containing sn-1 alkyl (C-16) and the sn-2 fatty acyl (>C-16) such as conjugate 1 were sparingly soluble. Conjugates 9a-c,e were almost completely solubilized in water by shaking. However, a large portion of conjugates 9d and 9f in water by shaking exist in micelles with mean diameters ranging 7.0-55.2 nm. The partition coefficients (1-octanol/PBS) of the water-soluble conjugates were about 9-18 times greater than that of ara-C. A single dose (300 mg/kg) of conjugates 9d and 9f produced a significant increase in life span (ILS 206 to >543%) with 17-67% long-term survivors (>45 days) in mice bearing ip-implanted L1210 lymphoid leukemia. These results were comparable to those of the previous conjugate 1 and Cytoros (2). In contrast, conjugates 9a-c,e at single doses were less effective (ILS 69-178% with no long-term survivors). However, two (qd, 1, 7) or three (qd 1, 5, 9) divided doses of these conjugates were found to be as effective as a single dose of the previous conjugates. The three divided doses (150 mg/kg per day) of conjugates 9d, 9e, and 9f produced a remarkable antitumor activity in L1210 leukemic mice (ILS >350% with >50% long-term survivors). Because of the convenient formulation and the significant antitumor activities, the water-soluble conjugates 9d, 9e, and 9f warrant further investigation.