2,6-diisopropylphenyl {[4-(3-methoxyphenyl)piperidin-4-yl]-carbonyl}sulfamate | 1224432-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2,6-diisopropylphenyl {[4-(3-methoxyphenyl)piperidin-4-yl]-carbonyl}sulfamate
• 英文别名: 2,6-Diisopropylphenyl{[4-(3-Methoxyphenyl)Piperidin-4-yl]-carbonyl}sulfamate；[2,6-di(propan-2-yl)phenyl] N-[4-(3-methoxyphenyl)piperidine-4-carbonyl]sulfamate
• CAS: 1224432-16-9
• 化学式: C₂₅H₃₄N₂O₅S
• 分子量: 474.621
• InChiKey: QKXBUBDAYKGQEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氯-4-甲基嘧啶 、 2,6-diisopropylphenyl {[4-(3-methoxyphenyl)piperidin-4-yl]-carbonyl}sulfamate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以72%的产率得到2,6-diisopropylphenyl {[4-(3-methoxyphenyl)-1-(4-methylpyrimidin-2-yl)piperidin-4-yl]carbonyl}sulfamate
  参考文献：
  名称：

  A Novel Class of Antihyperlipidemic Agents with Low Density Lipoprotein Receptor Up-Regulation via the Adaptor Protein Autosomal Recessive Hypercholesterolemia

  摘要：

  We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator, and describe the discovery of a novel class of up-regulators of LDL-R. Replacement the methylene urea linker in compound 2 with an acylsulfonamide linker kept a potent LDL-R up-regulatory activity, and subsequent optimization work gave compound 39 as a highly potent LDL-R up-regulator (39; EC25 = 0.047 mu M). Compound 39 showed no ACAT inhibitory activity even at 1 mu M. The sodium salts of compound 39 reduced plasma total and LDL cholesterol levels in a dose-dependent manner in an experimental animal model of hyperlipidemia. Moreover, we revealed in this study using RNA interference that autosomal recessive hypercholesterolemia (ARH), an adaptor protein of LDL-R, is essential for compound 39 up-regulation of LDL-R expression.

  DOI：

  10.1021/jm901909p
• 作为产物：
  描述：

  2,6-diisopropylphenyl {[1-(diphenylmethyl)-4-(3-methoxyphenyl)-piperidin-4-yl]carbonyl}sulfamate 在 20 % Pd(OH)2/C 、 氢气 、 甲烷 作用下， 以 N,N-二甲基甲酰胺 、 1,4-二氧六环 为溶剂， 反应 1.5h， 以31%的产率得到2,6-diisopropylphenyl {[4-(3-methoxyphenyl)piperidin-4-yl]-carbonyl}sulfamate
  参考文献：
  名称：

  A Novel Class of Antihyperlipidemic Agents with Low Density Lipoprotein Receptor Up-Regulation via the Adaptor Protein Autosomal Recessive Hypercholesterolemia

  摘要：

  We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator, and describe the discovery of a novel class of up-regulators of LDL-R. Replacement the methylene urea linker in compound 2 with an acylsulfonamide linker kept a potent LDL-R up-regulatory activity, and subsequent optimization work gave compound 39 as a highly potent LDL-R up-regulator (39; EC25 = 0.047 mu M). Compound 39 showed no ACAT inhibitory activity even at 1 mu M. The sodium salts of compound 39 reduced plasma total and LDL cholesterol levels in a dose-dependent manner in an experimental animal model of hyperlipidemia. Moreover, we revealed in this study using RNA interference that autosomal recessive hypercholesterolemia (ARH), an adaptor protein of LDL-R, is essential for compound 39 up-regulation of LDL-R expression.

  DOI：

  10.1021/jm901909p