3-(4-isobutoxycarbonyl)phenoxy-1-bromoacetone | 1025828-97-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-isobutoxycarbonyl)phenoxy-1-bromoacetone
• 英文别名: 2-methylpropyl 4-(3-bromo-2-hydroxypropoxy)benzoate
• CAS: 1025828-97-0
• 化学式: C₁₄H₁₉BrO₄
• 分子量: 331.206
• InChiKey: JBHUREOOSHRDQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-isobutoxycarbonyl)phenoxy-1-bromoacetone 在 2,6-二甲基吡啶 、 chromium(VI) oxide 、 硫酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 8-<<3-(p-isobutoxycarbonyl)phenoxy-2-oxo-propyl>thio> adenosine
  参考文献：
  名称：

  8-Substituted purine derivatives: a new class of lipid-lowering agents

  摘要：

  A series of purine derivatives have been prepared and their in vivo abilities to lower plasma total cholesterol and triglyceride levels, and to elevate high density lipoprotein (HDL) cholesterol levels in hyperlipemic rats have been tested. Some compounds, among which 8-{2-(R)-hydroxy-3-[(p-isobutoxycarbonyl)phenoxy]propylthio}adenosine 31, 8-{3-[(p-isobutoxy carbonyl)phenoxy]-2-oxopropylthio} adenosine 33 and 8-{3-[(p-isobutoxycarbonyl)phenoxy]-2-hydrazonecarboxamidepropylthio} adenosine 36 appear to be the most interesting, have been found to have both the desired profile of activity and no hepatotoxicity, when administered po at 50, 100 or 300 mg/kg. Compounds 31, 33 and 36, orally tested at the same doses in the 15-d test, lower triglyceride and VLDL/LDL (very low density lipoprotein/low density lipoprotein) cholesterol levels by 10-33% and 13-46%, respectively, and increase HDL-associated cholesterol levels by 10-32%. These molecules have been chosen for further pharmacological and toxicological evaluations.

  DOI：

  10.1016/0223-5234(94)90098-1
• 作为产物：
  描述：

  4-isobutoxycarbonylphenoxy-2,3-epoxypropane 在 氢溴酸 、 溶剂黄146 作用下， 生成 3-(4-isobutoxycarbonyl)phenoxy-1-bromoacetone
  参考文献：
  名称：

  8-Substituted purine derivatives: a new class of lipid-lowering agents

  摘要：

  A series of purine derivatives have been prepared and their in vivo abilities to lower plasma total cholesterol and triglyceride levels, and to elevate high density lipoprotein (HDL) cholesterol levels in hyperlipemic rats have been tested. Some compounds, among which 8-{2-(R)-hydroxy-3-[(p-isobutoxycarbonyl)phenoxy]propylthio}adenosine 31, 8-{3-[(p-isobutoxy carbonyl)phenoxy]-2-oxopropylthio} adenosine 33 and 8-{3-[(p-isobutoxycarbonyl)phenoxy]-2-hydrazonecarboxamidepropylthio} adenosine 36 appear to be the most interesting, have been found to have both the desired profile of activity and no hepatotoxicity, when administered po at 50, 100 or 300 mg/kg. Compounds 31, 33 and 36, orally tested at the same doses in the 15-d test, lower triglyceride and VLDL/LDL (very low density lipoprotein/low density lipoprotein) cholesterol levels by 10-33% and 13-46%, respectively, and increase HDL-associated cholesterol levels by 10-32%. These molecules have been chosen for further pharmacological and toxicological evaluations.

  DOI：

  10.1016/0223-5234(94)90098-1

文献信息

• 8-Substituted purine derivatives: a new class of lipid-lowering agents
  作者：E Vanotti、M Bani、D Favara、M Gobetti、M Lombroso、S Magnetti、V Olgiati、M Palladino、GC Tonon

  DOI：10.1016/0223-5234(94)90098-1

  日期：1994.1

  A series of purine derivatives have been prepared and their in vivo abilities to lower plasma total cholesterol and triglyceride levels, and to elevate high density lipoprotein (HDL) cholesterol levels in hyperlipemic rats have been tested. Some compounds, among which 8-2-(R)-hydroxy-3-[(p-isobutoxycarbonyl)phenoxy]propylthio}adenosine 31, 8-3-[(p-isobutoxy carbonyl)phenoxy]-2-oxopropylthio} adenosine 33 and 8-3-[(p-isobutoxycarbonyl)phenoxy]-2-hydrazonecarboxamidepropylthio} adenosine 36 appear to be the most interesting, have been found to have both the desired profile of activity and no hepatotoxicity, when administered po at 50, 100 or 300 mg/kg. Compounds 31, 33 and 36, orally tested at the same doses in the 15-d test, lower triglyceride and VLDL/LDL (very low density lipoprotein/low density lipoprotein) cholesterol levels by 10-33% and 13-46%, respectively, and increase HDL-associated cholesterol levels by 10-32%. These molecules have been chosen for further pharmacological and toxicological evaluations.
• Novel aryloxyalkylthioimidazoles as inhibitors of acyl-CoA: cholesterol-O-acyltransferase
  作者：M Bani、R Bormetti、W Ceccarelli、R Fiocchi、M Gobetti、M Lombroso、S Magnetti、V Olgiati、M Palladino、M Villa、E Vanotti

  DOI：10.1016/0223-5234(96)88207-9

  日期：1995.1

  A series of aryloxyalkylthioimidazoles have been synthesized and evaluated for their ability,to interfere with the enzyme acyl-CoA (cholesterol-O-acyltransferase) (ACAT, EC 2.3.1.26). Most of the molecules possessed a good in vitro ACAT inhibitory activity with IC50 values ranging between 0.1 and 2.0 mu M Some of them, eg, 2-5-[(4-isobutoxycarbonyl)phenoxy]-pentylthio} -4,5-diphenylimidazole 13, 2-3-[(4-isobutoxycarbonyl)phenoxy]-2-oximinopropylthio}-4,5-diphenylimidazole 21, 2-3-[(4-isobutoxycarbonyl)phenoxy]-2-hydrazonecarboxamidepropylthio) -4,5-diphenylimidazole 26, 2-[5-(2-pyridoxy)-pentylthio]-4,5-diphenylimidazole 40 and 2-5-[(3,5-diterbutyl-4-hydroxy)phenylthio]pentylthio}-4,5-diphenylimidazole 42, were more potent (range of activity 10-90 nM). They were also more potent with respect to the reference CI-976. When administered orally in hyperlipemic rats, at 10 and 50 mg/kg doses, some representative compounds, like 2-3-[(4-isobutoxycarbonyl)phenoxy]-2-hydroxypropylthio}-4,5-diphenylimidazole 1, 13 and 26, reduced VLDL/LDL-associated cholesterol levels by 30-50% and increased HDL cholesterol levels by 15-50%. In addition, liver accumulation of esterified cholesterol was counteracted (50-80% reduction) and liver ACAT ex vivo activity was decreased by 70-85%. Finally, the good efficacy displayed in an endogenous model of hypertriglyceridemia strongly supports the hypothesis of a good systemic availability, which constitutes one of the principal properties of a valuable ACAT inhibitor.