3-{[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl]oxycarbonyl}propanoyl chloride | 66972-42-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3-{[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl]oxycarbonyl}propanoyl chloride
• 英文别名: 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydro-2H-chromen-6-yl 4-chloro-4-oxobutanoate；[2,5,7,8-Tetramethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-yl] 4-chloro-4-oxobutanoate
• CAS: 66972-42-7
• 化学式: C₃₃H₅₃ClO₄
• 分子量: 549.234
• InChiKey: BLNZIACHGFDABP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.2
• 重原子数：
  38
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl]oxycarbonyl}propanoyl chloride 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 ammonium formate 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 5.83h， 生成 (+/-)-7α,12α-dihydroxy-3α-(3-{[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl]oxycarbonyl}propanoyloxy)-5β-cholan-24-oic acid
  参考文献：
  名称：

  New propanoyloxy derivatives of 5β-cholan-24-oic acid as drug absorption modifiers

  摘要：

  A series of final twelve propanoyloxy derivatives of 5 beta-cholan-24-oic acid (O-propanoyl derivatives of cholic acid) as potential drug absorption modifiers (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by H-1 NMR, C-13 NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R-M) was determined. The hydrophobicity (log P), solubility (log S), polar surface area (PSA) and molar volume (MV) of the studied compounds were also calculated. All the target compounds were tested for their in vitro transdermal. penetration effect and as potential intestinal absorption enhancers. The cytotoxicity of all the evaluated compounds was evaluated against normal human skin fibroblast cells. Their anti-proliferative activity was also assessed against human cancer cell lines: T-lymphoblastic leukemia cell line and breast adenocarcinoma cell line. One compound showed selective cytotoxicity against human skin fibroblast cells and another compound possessed the highest cytotoxicity against all the tested cell lines. Only one compound expressed anti-proliferative effect on leukemia cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC50 > 37 mu M), indicating they would have moderate cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity/polarity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effect are discussed in this article. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2013.02.001
• 作为产物：
  描述：

  DL-α-生育酚 在 4-二甲氨基吡啶 、 草酰氯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 3-{[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl]oxycarbonyl}propanoyl chloride
  参考文献：
  名称：

  New propanoyloxy derivatives of 5β-cholan-24-oic acid as drug absorption modifiers

  摘要：

  A series of final twelve propanoyloxy derivatives of 5 beta-cholan-24-oic acid (O-propanoyl derivatives of cholic acid) as potential drug absorption modifiers (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by H-1 NMR, C-13 NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R-M) was determined. The hydrophobicity (log P), solubility (log S), polar surface area (PSA) and molar volume (MV) of the studied compounds were also calculated. All the target compounds were tested for their in vitro transdermal. penetration effect and as potential intestinal absorption enhancers. The cytotoxicity of all the evaluated compounds was evaluated against normal human skin fibroblast cells. Their anti-proliferative activity was also assessed against human cancer cell lines: T-lymphoblastic leukemia cell line and breast adenocarcinoma cell line. One compound showed selective cytotoxicity against human skin fibroblast cells and another compound possessed the highest cytotoxicity against all the tested cell lines. Only one compound expressed anti-proliferative effect on leukemia cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC50 > 37 mu M), indicating they would have moderate cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity/polarity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effect are discussed in this article. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2013.02.001

文献信息

• Polyphenolic Bioprecursors
  申请人：Delaire Sabine

  公开号：US20090215881A1

  公开（公告）日：2009-08-27

  Cosmetic and therapeutic, in particular dermatological bioprecursors have the formula [A] n —PP—[B] m wherein PP is a polyphenol radical in which each hydroxyl function is protected by a group A or a group B, A is a saturated or unsaturated, substituted or unsubstituted alkyl radical having 1 to 20 carbon atoms which is bonded to the polyphenol, n is an integer not less than 1, and B is a precursor of a biologically active molecule, which is also bonded to the polyphenol, and m is an integer also not less than 1.

  化妆品和治疗用途，特别是皮肤病学生物前体具有以下公式[A]n—PP—[B]m，其中PP是一个多酚基团，其中每个羟基功能都由基团A或基团B保护，A是一个饱和或不饱和的、取代或未取代的烷基基团，含有1至20个碳原子，与多酚结合，n是一个不小于1的整数，B是生物活性分子的前体，也与多酚结合，m也是一个不小于1的整数。
• New propanoyloxy derivatives of 5β-cholan-24-oic acid as drug absorption modifiers
  作者：Lenka Coufalová、Lech Mrózek、Lucie Rárová、Lukáš Plaček、Radka Opatřilová、Jiří Dohnal、Katarína Král’ová、Oldřich Paleta、Vladimír Král、Pavel Drašar、Josef Jampílek

  DOI：10.1016/j.steroids.2013.02.001

  日期：2013.5

  A series of final twelve propanoyloxy derivatives of 5 beta-cholan-24-oic acid (O-propanoyl derivatives of cholic acid) as potential drug absorption modifiers (skin penetration enhancers, intestinal absorption promoters) was generated by multistep synthesis. Structure confirmation of all generated compounds was accomplished by H-1 NMR, C-13 NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R-M) was determined. The hydrophobicity (log P), solubility (log S), polar surface area (PSA) and molar volume (MV) of the studied compounds were also calculated. All the target compounds were tested for their in vitro transdermal. penetration effect and as potential intestinal absorption enhancers. The cytotoxicity of all the evaluated compounds was evaluated against normal human skin fibroblast cells. Their anti-proliferative activity was also assessed against human cancer cell lines: T-lymphoblastic leukemia cell line and breast adenocarcinoma cell line. One compound showed selective cytotoxicity against human skin fibroblast cells and another compound possessed the highest cytotoxicity against all the tested cell lines. Only one compound expressed anti-proliferative effect on leukemia cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC50 > 37 mu M), indicating they would have moderate cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity/polarity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effect are discussed in this article. (C) 2013 Elsevier Inc. All rights reserved.