diethyl 2-(4-benzyloxyphenyl)-1-hydroxyiminoethylphosphonate | 84891-33-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: diethyl 2-(4-benzyloxyphenyl)-1-hydroxyiminoethylphosphonate
• 英文别名: diethyl 2-(4-benzyloxyphenyl)-1-(hydroxyimino)ethylphosphonate；Diethyl 2-(4-benzyloxyphenyl)-1-(hydroxyimino)ethylphosphonate；N-[1-diethoxyphosphoryl-2-(4-phenylmethoxyphenyl)ethylidene]hydroxylamine
• CAS: 84891-33-8
• 化学式: C₁₉H₂₄NO₅P
• 分子量: 377.377
• InChiKey: FHBGSSSCGXEPIE-UHFFFAOYSA-N

物化性质

• 沸点：
  520.1±52.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  77.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl 2-(4-benzyloxyphenyl)-1-hydroxyiminoethylphosphonate 在 palladium 10% on activated carbon 、 copper diacetate 、 nickel dichloride 吡啶 、 氢氧化钾 、 sodium tetrahydroborate 、 三甲基溴硅烷 、 四丁基氟化铵 、 水 、 氢气 、 碘 、 bis(pyridine)iodonium tetrafluoroborate 、 三乙胺 、 甲胺 、 三氟乙酸 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 111.33h， 生成 1-amino-2-[3,5-diiodo-4-(4'-hydroxy-3'-iodophenoxy)]phenylethylphosphonic acid
  参考文献：
  名称：

  [EN] NOVEL PHOSPHORUS-CONTAINING THYROMIMETICS
  [FR] NOUVELLES SUBSTANCES THYROMIMETIQUES CONTENANT DU PHOSPHORE

  摘要：

  公开号：

  WO2005051298A3
• 作为产物：
  描述：

  4-苄氧基苯乙酰氯 在 盐酸羟胺 作用下， 以 四氢呋喃 、 吡啶 、 正己烷 为溶剂， 反应 88.0h， 生成 diethyl 2-(4-benzyloxyphenyl)-1-hydroxyiminoethylphosphonate
  参考文献：
  名称：

  [EN] NOVEL PHOSPHORUS-CONTAINING THYROMIMETICS
  [FR] NOUVELLES SUBSTANCES THYROMIMETIQUES CONTENANT DU PHOSPHORE

  摘要：

  公开号：

  WO2005051298A3

文献信息

• Novel Phosphinic Acid-Containing Thyromimetics
  申请人：Erion Mark D.

  公开号：US20090028925A1

  公开（公告）日：2009-01-29

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有磷酸基T3拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟
• Novel Phosphorus-Containing Thyromimetics
  申请人：Erion Mark D.

  公开号：US20100081634A1

  公开（公告）日：2010-04-01

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有膦酸的T3模拟物化合物及其单酯、立体异构体、药学上可接受的盐、共晶体和前药及其药学上可接受的盐和共晶体，以及它们的制备和用于预防和/或治疗代谢性疾病，如肥胖症、NASH、高胆固醇血症和高脂血症，以及相关疾病，如动脉粥样硬化、冠心病、糖耐量受损、代谢综合征X和糖尿病的用途。
• Novel phosphorus-containing thyromimetics
  申请人：Erion D. Mark

  公开号：US20060046980A1

  公开（公告）日：2006-03-02

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有膦酸基的T3类似物化合物及其单酯体、立体异构体、药学上可接受的盐、共晶体和其前药物，以及前药物的药学上可接受的盐和共晶体，以及它们的制备和用于预防和/或治疗代谢性疾病，如肥胖症、NASH、高胆固醇血症和高脂血症，以及相关疾病，如动脉粥样硬化、冠心病、糖耐量受损、代谢综合征x和糖尿病。
• Phosphorus-containing thyromimetics
  申请人：Metabasis Therapeutics, Inc.

  公开号：US07514419B2

  公开（公告）日：2009-04-07

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有膦酸的T3类似物和其单酯化合物、立体异构体、药学上可接受的盐、共晶体以及其前药和前药的药学上可接受的盐和共晶体，以及它们的制备和用于预防和/或治疗代谢性疾病，如肥胖症、NASH、高胆固醇血症和高脂血症，以及相关疾病，如动脉粥样硬化、冠心病、糖耐量受损、代谢综合征和糖尿病的用途。
• 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.