(R,S)-(1α,4β)-1-methyl-4-<(tetrahydro-2H-pyran-2-yl)oxy>cyclohexanecarboxaldehyde | 157555-32-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: (R,S)-(1α,4β)-1-methyl-4-<(tetrahydro-2H-pyran-2-yl)oxy>cyclohexanecarboxaldehyde
• CAS: 157555-32-3
• 化学式: C₁₃H₂₂O₃
• 分子量: 226.316
• InChiKey: AZOJAACJKJLTSR-DHKXFDHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (R,S)-(1α,4β)-1-methyl-4-<(tetrahydro-2H-pyran-2-yl)oxy>cyclohexanecarboxaldehyde 在 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 、 sodium methylate 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.25h， 生成 d,l-<1α(E),4β>-2-<<1,1-dimethyl-5-<3-<2-<1-methyl-4-<(tetrahydro-2H-pyran-2-yl)oxy>cyclohexyl>ethenyl>phenyl>pentyl>oxy>tetrahydro-2H-pyran
  参考文献：
  名称：

  Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription

  摘要：

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.

  DOI：

  10.1021/jm00041a013
• 作为产物：
  描述：

  1-methyl-t-4-(2-tetrahydropyranyloxy)-r-1-cyclohexanemethanol 在 吡啶 、 三氧化硫 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.75h， 以92%的产率得到(R,S)-(1α,4β)-1-methyl-4-<(tetrahydro-2H-pyran-2-yl)oxy>cyclohexanecarboxaldehyde
  参考文献：
  名称：

  Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription

  摘要：

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.

  DOI：

  10.1021/jm00041a013

文献信息

• Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription
  作者：Scott D. Larsen、Charles H. Spilman、Yoshi Yagi、Dac M. Dinh、Karen L. Hart、Gerard F. Hess

  DOI：10.1021/jm00041a013

  日期：1994.7

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.