2,6-diisopropylphenyl ({4-(3-methoxyphenyl)-1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}carbonyl)sulfamate | 1224432-21-6

• 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)-1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}carbonyl)sulfamate
• 英文别名: [2,6-di(propan-2-yl)phenyl] N-[4-(3-methoxyphenyl)-1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidine-4-carbonyl]sulfamate
• CAS: 1224432-21-6
• 化学式: C₃₀H₃₅F₃N₄O₅S
• 分子量: 620.693
• InChiKey: IYTYFFFPCZGGAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,6-diisopropylphenyl {[4-(3-methoxyphenyl)piperidin-4-yl]-carbonyl}sulfamate 、 2-氯-4-三氟甲基嘧啶 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到2,6-diisopropylphenyl ({4-(3-methoxyphenyl)-1-[4-(trifluoromethyl)pyrimidin-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

文献信息

• A Novel Class of Antihyperlipidemic Agents with Low Density Lipoprotein Receptor Up-Regulation <i>via</i> the Adaptor Protein Autosomal Recessive Hypercholesterolemia
  作者：Shigehiro Asano、Hitoshi Ban、Norie Tsuboya、Shinsaku Uno、Kouichi Kino、Katsuhisa Ioriya、Masafumi Kitano、Yoshihide Ueno

  DOI：10.1021/jm901909p

  日期：2010.4.22

  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.