4-Bromo-2-ethyl-1-(methoxymethoxy)benzene | 1085957-45-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-Bromo-2-ethyl-1-(methoxymethoxy)benzene
• CAS: 1085957-45-4
• 化学式: C₁₀H₁₃BrO₂
• 分子量: 245.116
• InChiKey: FLTGDCRXCKWXSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Bromo-2-ethyl-1-(methoxymethoxy)benzene 、 2,6-dimethyl-4-triisopropylsilyloxybenzaldehyde 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 生成 [2,6-Dimethyl-4-tri(propan-2-yl)silyloxyphenyl]-[3-ethyl-4-(methoxymethoxy)phenyl]methanol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Series of Liver-Selective Phosphonic Acid Thyroid Hormone Receptor Agonists and Their Prodrugs

  摘要：

  Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TR beta(1), K-i < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T-3, PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED50 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.

  DOI：

  10.1021/jm800824d

文献信息

• [EN] ANALOGUES OF VITAMIN D<br/>[FR] ANALOGUES DE LA VITAMINE D
  申请人：GALDERMA RES & DEV S N C SOPHI

  公开号：WO2004020379A1

  公开（公告）日：2004-03-11

  The invention relates, as new and useful industrial products, to biaromatic compounds, which are analogues of vitamin D, of general formula (I): Q,A~R 2 R4 R~ R 4 T~B OH (I) HO and to their method of preparation and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions.

  该发明涉及一种新型和有用的工业产品，即类似维生素D的双芳香化合物，其一般式为（I）：Q，A~R 2 R4 R~ R 4 T~B OH（I）HO，以及它们的制备方法和它们在用于人类或兽医药物的制药组合物中的用途，或者在化妆品组合物中的用途。
• Novel vitamin D analogues
  申请人：Biadatti Thibaud

  公开号：US20050182144A1

  公开（公告）日：2005-08-18

  Novel biaromatic vitamin D analogues have the general formula (I): and are suited for a wide variety of pharmaceutical applications, whether in human or veterinary medicine, and also for cosmetic applications.

  新型的双芳基维生素D类似物具有通用的化学式（I），适用于各种药物应用，无论是人类医学、兽医学还是化妆品应用。
• ANALOGUES OF VITAMIN D
  申请人：Galderma Research & Development, S.N.C.

  公开号：EP1537065A1

  公开（公告）日：2005-06-08
• US7312249B2
  申请人：——

  公开号：US7312249B2

  公开（公告）日：2007-12-25
• Synthesis and Biological Evaluation of a Series of Liver-Selective Phosphonic Acid Thyroid Hormone Receptor Agonists and Their Prodrugs
  作者：Serge H. Boyer、Hongjian Jiang、Jason D. Jacintho、Mali Venkat Reddy、Haiqing Li、Wenyu Li、Jennifer L. Godwin、William G. Schulz、Edward E. Cable、Jinzhao Hou、Rongrong Wu、James M. Fujitaki、Scott J. Hecker、Mark D. Erion

  DOI：10.1021/jm800824d

  日期：2008.11.27

  Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TR beta(1), K-i < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T-3, PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED50 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.