[3,5-dibromo-4-(4'-hydroxy-3'-isopropylphenoxy)phenoxy]methylphosphonic acid | 852947-80-9

• 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: [3,5-dibromo-4-(4'-hydroxy-3'-isopropylphenoxy)phenoxy]methylphosphonic acid
• 英文别名: [3,5-dibromo-4-(3'-iso-propyl-4'-hydroxyphenoxy)phenoxy]methylphosphonic acid；[3,5-Dibromo-4-(4''-hydroxy-3''-isopropylphenoxy)phenoxy]methylphosphonicAcid；[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenoxy]methylphosphonic acid
• CAS: 852947-80-9
• 化学式: C₁₆H₁₇Br₂O₆P
• 分子量: 496.089
• InChiKey: KHQSAJNTRGEQEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-[2,6-Dibromo-4-(diethoxyphosphorylmethoxy)phenoxy]-2-propan-2-ylphenol 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 生成 [3,5-dibromo-4-(4'-hydroxy-3'-isopropylphenoxy)phenoxy]methylphosphonic acid
  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
• [EN] PHOSPHORUS-CONTAINING THYROID HORMONE RECEPTOR AGONISTS AND METHODS OF USE<br/>[FR] AGONISTES DES RÉCEPTEURS DES HORMONES THYROÏDIENNES CONTENANT DU PHOSPHORE ET MÉTHODES D'UTILISATION
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2011038207A1

  公开（公告）日：2011-03-31

  The present invention relates to sulfonic acid containing compounds that bind to thyroid receptors in the liver. Activation of these receptors results in modulation of gene expression of genes regulated by thyroid hormones. The compounds can be used to treat diseases and disorders including metabolic diseases such as NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, and metabolic syndrome X.

  本发明涉及含有磺酸基团的化合物，能够与肝脏中的甲状腺受体结合。激活这些受体会导致对甲状腺激素调控的基因表达的调节。这些化合物可用于治疗包括NASH、高胆固醇血症和高脂血症在内的代谢性疾病，以及相关病症，如动脉粥样硬化、冠心病、糖耐量受损和代谢综合征X。
• 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。
• Method of treating glycogen storage disease
  申请人：Viking Therapeutics, Inc.

  公开号：US11202789B2

  公开（公告）日：2021-12-21

  The present disclosure provides methods and compositions for the treatment of hepatic symptoms of glycogen storage diseases through the administration of thyroid hormone receptor agonists. The methods and compositions provided herein are useful in the treatment of hyperlipidemia, hypercholesterolemia, hepatic steatosis, cardiomegaly, hepatomegaly, hepatic fibrosis, and cirrhosis associated with glycogen storage diseases (GSD) and defects of glycogen metabolism. Said compounds may also be useful in the prevention of GSD-related hepatocellular adenoma and hepatocellular carcinoma.

  本公开提供了通过服用甲状腺激素受体激动剂治疗糖原贮积病的肝脏症状的方法和组合物。本文提供的方法和组合物可用于治疗与糖原贮积病（GSD）和糖原代谢缺陷相关的高脂血症、高胆固醇血症、肝脂肪变性、心脏肿大、肝肿大、肝纤维化和肝硬化。上述化合物还可用于预防与 GSD 相关的肝细胞腺瘤和肝细胞癌。