methyl (3α,7α,12α)-tris(methoxyethoxymethyl)-cholate | 943135-89-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: methyl (3α,7α,12α)-tris(methoxyethoxymethyl)-cholate
• 英文别名: methyl (4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-tris(2-methoxyethoxymethoxy)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 943135-89-5
• 化学式: C₃₇H₆₆O₁₁
• 分子量: 686.924
• InChiKey: HONDELFBPBDNKB-JBPAQATLSA-N

物化性质

• 沸点：
  664.7±55.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  48
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl (3α,7α,12α)-tris(methoxyethoxymethyl)-cholate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以45%的产率得到(3α,7α,12α)-tris(methoxyethoxymethyl)-5β-cholestan-24-ol
  参考文献：
  名称：

  Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors

  摘要：

  The enzyme alpha-methylacyl-CoA racemase (AMACR) is overexpressed in prostate, colon, and other cancers and has been partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene. Analogs of the natural substrate branched chain alpha-methylacyl coenzyme A esters, possessing one or more beta-fluorine atoms, have been synthesized using Wittig, conjugate addition, and asymmetric aldol reactions and found to be reversible competitive inhibitors. Each diastereomer of the previously reported inhibitor ibuprofenoyl-CoA was also tested. The compounds had K-i values of 0.9-20 mu M and are the most potent inhibitors yet known. The presence of beta-fluorine on the alpha-methyl group or the acyl chain results in a significant lowering of the K-i value compared with nonfluorinated analogs, and this is attributed to a lowering of the pK(a) of the alpha-proton, facilitating enolization and binding. Several of the CoA ester inhibitors were formed by incubating the free carboxylic acid precursors with cell free extracts and CoA. alpha-Trifluoromethyltetradecanoic acid, the precursor to the most potent inhibitor, was shown to inhibit growth of cancer cell lines PC3, CWR22 Rv1, and Du145 in a dose-dependent manner and could be related to the expression level of AMACR.

  DOI：

  10.1021/jm0702377
• 作为产物：
  描述：

  胆酸 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl (3α,7α,12α)-tris(methoxyethoxymethyl)-cholate
  参考文献：
  名称：

  Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors

  摘要：

  The enzyme alpha-methylacyl-CoA racemase (AMACR) is overexpressed in prostate, colon, and other cancers and has been partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene. Analogs of the natural substrate branched chain alpha-methylacyl coenzyme A esters, possessing one or more beta-fluorine atoms, have been synthesized using Wittig, conjugate addition, and asymmetric aldol reactions and found to be reversible competitive inhibitors. Each diastereomer of the previously reported inhibitor ibuprofenoyl-CoA was also tested. The compounds had K-i values of 0.9-20 mu M and are the most potent inhibitors yet known. The presence of beta-fluorine on the alpha-methyl group or the acyl chain results in a significant lowering of the K-i value compared with nonfluorinated analogs, and this is attributed to a lowering of the pK(a) of the alpha-proton, facilitating enolization and binding. Several of the CoA ester inhibitors were formed by incubating the free carboxylic acid precursors with cell free extracts and CoA. alpha-Trifluoromethyltetradecanoic acid, the precursor to the most potent inhibitor, was shown to inhibit growth of cancer cell lines PC3, CWR22 Rv1, and Du145 in a dose-dependent manner and could be related to the expression level of AMACR.

  DOI：

  10.1021/jm0702377