(1S,3R,4S,5R,6R,7R)-1-((4S,5R)-4-Acetoxy-5-methyl-3-methylene-6-phenyl-hexyl)-6-((E)-(4S,6S)-4,6-dimethyl-oct-2-enoyloxy)-4,7-dihydroxy-3-(trifluoromethanesulfonylamino-methyl)-2,8-dioxa-bicyclo[3.2.1]octane-4,5-dicarboxylic acid | 175168-99-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,3R,4S,5R,6R,7R)-1-((4S,5R)-4-Acetoxy-5-methyl-3-methylene-6-phenyl-hexyl)-6-((E)-(4S,6S)-4,6-dimethyl-oct-2-enoyloxy)-4,7-dihydroxy-3-(trifluoromethanesulfonylamino-methyl)-2,8-dioxa-bicyclo[3.2.1]octane-4,5-dicarboxylic acid
• 英文别名: (1S,3R,4S,5R,6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-[(E,4S,6S)-4,6-dimethyloct-2-enoyl]oxy-4,7-dihydroxy-3-[(trifluoromethylsulfonylamino)methyl]-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid
• CAS: 175168-99-7
• 化学式: C₃₆H₄₈F₃NO₁₄S
• 分子量: 807.837
• InChiKey: XABUMMROFYVTIR-KLNZUXGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  55
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  241
• 氢给体数：
  5
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  (1S,3R,4S,5R,6R,7R)-1-((4S,5R)-4-Acetoxy-5-methyl-3-methylene-6-phenyl-hexyl)-6-((E)-(4S,6S)-4,6-dimethyl-oct-2-enoyloxy)-4,7-dihydroxy-3-(trifluoromethanesulfonylamino-methyl)-2,8-dioxa-bicyclo[3.2.1]octane-4,5-dicarboxylic acid 在 N-甲基羟胺盐酸盐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以52%的产率得到(1S,3R,4S,5R,6R,7R)-1-((4S,5R)-4-Acetoxy-5-methyl-3-methylene-6-phenyl-hexyl)-4,6,7-trihydroxy-3-(trifluoromethanesulfonylamino-methyl)-2,8-dioxa-bicyclo[3.2.1]octane-4,5-dicarboxylic acid
  参考文献：
  名称：

  The Squalestatins:  Inhibitors of Squalene Synthase. Enzyme Inhibitory Activities and in Vivo Evaluation of C3-Modified Analogues

  摘要：

  Squalestatin analogues modified at C3 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase in vitro. While the 4,6-dimethyloctenoate ester group at C6 was maintained, a number of modifications to the C3 carboxylic acid were well tolerated. However, in the absence of the C6 ester group, similar modifications to the C3 carboxyl group caused loss of activity. Selected compounds were evaluated for their ability to inhibit cholesterol biosynthesis in vivo in rats 1 and 6 h postadministration. Analogues of squalestatin 1 (S1) modified at C3 were found to possess a shorter duration of effect in vivo which is reflected in their substantially reduced ability to lower serum cholesterol levels in marmosets. Significant cholesterol lowering (up to 62%) for the C3 hydroxymethyl analogue Ib was observed only; when this compound was dosed three times a day for 3 days.

  DOI：

  10.1021/jm950893j
• 作为产物：
  描述：

  ditert-butyl (1S,3R,4S,5R,6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-3-(aminomethyl)-7-[tert-butyl(dimethyl)silyl]oxy-6-[(E,4S,6S)-4,6-dimethyloct-2-enoyl]oxy-4-hydroxy-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylate 在 2,4,6-三甲基吡啶 、 盐酸 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 11.33h， 生成 (1S,3R,4S,5R,6R,7R)-1-((4S,5R)-4-Acetoxy-5-methyl-3-methylene-6-phenyl-hexyl)-6-((E)-(4S,6S)-4,6-dimethyl-oct-2-enoyloxy)-4,7-dihydroxy-3-(trifluoromethanesulfonylamino-methyl)-2,8-dioxa-bicyclo[3.2.1]octane-4,5-dicarboxylic acid
  参考文献：
  名称：

  The Squalestatins:  Inhibitors of Squalene Synthase. Enzyme Inhibitory Activities and in Vivo Evaluation of C3-Modified Analogues

  摘要：

  Squalestatin analogues modified at C3 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase in vitro. While the 4,6-dimethyloctenoate ester group at C6 was maintained, a number of modifications to the C3 carboxylic acid were well tolerated. However, in the absence of the C6 ester group, similar modifications to the C3 carboxyl group caused loss of activity. Selected compounds were evaluated for their ability to inhibit cholesterol biosynthesis in vivo in rats 1 and 6 h postadministration. Analogues of squalestatin 1 (S1) modified at C3 were found to possess a shorter duration of effect in vivo which is reflected in their substantially reduced ability to lower serum cholesterol levels in marmosets. Significant cholesterol lowering (up to 62%) for the C3 hydroxymethyl analogue Ib was observed only; when this compound was dosed three times a day for 3 days.

  DOI：

  10.1021/jm950893j

文献信息

• The Squalestatins:  Inhibitors of Squalene Synthase. Enzyme Inhibitory Activities and <i>in</i> <i>Vivo</i> Evaluation of C3-Modified Analogues
  作者：Panayiotis A. Procopiou、Brian Cox、Barrie E. Kirk、Michael G. Lester、Alun D. McCarthy、Meenu Sareen、Peter J. Sharratt、Michael A. Snowden、Stephen J. Spooner、Nigel S. Watson、Julia Widdowson

  DOI：10.1021/jm950893j

  日期：1996.1.1

  Squalestatin analogues modified at C3 were prepared and evaluated for their ability to inhibit rat liver microsomal squalene synthase in vitro. While the 4,6-dimethyloctenoate ester group at C6 was maintained, a number of modifications to the C3 carboxylic acid were well tolerated. However, in the absence of the C6 ester group, similar modifications to the C3 carboxyl group caused loss of activity. Selected compounds were evaluated for their ability to inhibit cholesterol biosynthesis in vivo in rats 1 and 6 h postadministration. Analogues of squalestatin 1 (S1) modified at C3 were found to possess a shorter duration of effect in vivo which is reflected in their substantially reduced ability to lower serum cholesterol levels in marmosets. Significant cholesterol lowering (up to 62%) for the C3 hydroxymethyl analogue Ib was observed only; when this compound was dosed three times a day for 3 days.