1,3-Dibromo-5-(bromomethyl)-2-(4-methoxy-3-propan-2-ylphenoxy)benzene | 877218-18-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,3-Dibromo-5-(bromomethyl)-2-(4-methoxy-3-propan-2-ylphenoxy)benzene
• CAS: 877218-18-3
• 化学式: C₁₇H₁₇Br₃O₂
• 分子量: 493.033
• InChiKey: QWNPQDLYHHVFMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  甲基膦酸二乙酯 、 1,3-Dibromo-5-(bromomethyl)-2-(4-methoxy-3-propan-2-ylphenoxy)benzene 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 以43%的产率得到1,3-Dibromo-5-(2-diethoxyphosphorylethyl)-2-(4-methoxy-3-propan-2-ylphenoxy)benzene
  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
• 作为产物：
  描述：

  3,5-dibromo-4-(4-methoxy-3-isopropylphenoxy)benzylalcohol 在 四溴化碳 、 三苯基膦 作用下， 以 乙醚 为溶剂， 生成 1,3-Dibromo-5-(bromomethyl)-2-(4-methoxy-3-propan-2-ylphenoxy)benzene
  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

• 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 PHOSPHINIC ACID-CONTAINING THYROMIMETICS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP1890768A2

  公开（公告）日：2008-02-27
• NOVEL PHOSPHORUS-CONTAINING THYROMIMETICS
  申请人：Metabasis Therapeutics, Inc.

  公开号：EP1891080A2

  公开（公告）日：2008-02-27
• US7514419B2
  申请人：——

  公开号：US7514419B2

  公开（公告）日：2009-04-07
• [EN] NOVEL PHOSPHORUS-CONTAINING THYROMIMETICS<br/>[FR] NOUVELLES SUBSTANCES THYROMIMETIQUES CONTENANT DU PHOSPHORE
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2006128055A2

  公开（公告）日：2006-11-30

  [EN] 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.
  [FR] L'invention concerne des composés de mimétiques T3 contenant de l'acide phosphonique et des monoesters de ceux-ci, des stéréo-isomères, des sels pharmaceutiquement acceptables, des cocristaux et des promédicaments de ces composés, ainsi que des sels pharmaceutiquement acceptables et des cocristaux de ces promédicaments. L'invention concerne également leur préparation et leurs utilisations pour prévenir et/ou traiter des maladies métaboliques telles que l'obésité, la stéato-hépatite non alcoolique, l'hypercholestérolémie et l'hyperlipidémie, ainsi que des troubles associés comme l'athérosclérose, la maladie coronarienne, l'intolérance au glucose, le syndrome métabolique ou syndrome X et le diabète.