trifluoromethanesulfonic acid 4-(3-isopropyl-4-methoxymethoxybenzyl)-3,5-dimethylphenyl ester | 848442-44-4

• 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: trifluoromethanesulfonic acid 4-(3-isopropyl-4-methoxymethoxybenzyl)-3,5-dimethylphenyl ester
• 英文别名: trifluoromethanesulfonic acid 3,5-dimethyl-4-(3'-iso-propyl-4'-(methoxymethoxy)benzyl)phenyl ester；3,5-dimethyl-4-(4'-methoxymethoxy-3'-iso-propylbenzyl)-trifluoromethanesulfonyloxyphenyl；3,5-dimethyl-4-(4'-methoxymethoxy-3'-iso-propylbenzyl)trifluoromethanesulfonyloxyphenyl；3,5-Dimethyl-4-(3'-iso-propyl-4'-methoxymethoxy-benzyl)phenyl trifluoromethanesulfonate；[4-[[4-(methoxymethoxy)-3-propan-2-ylphenyl]methyl]-3,5-dimethylphenyl] trifluoromethanesulfonate
• CAS: 848442-44-4
• 化学式: C₂₁H₂₅F₃O₅S
• 分子量: 446.488
• InChiKey: SUZHATSZZZCOEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  trifluoromethanesulfonic acid 4-(3-isopropyl-4-methoxymethoxybenzyl)-3,5-dimethylphenyl ester 在 哌啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 sodium tetrahydroborate 、 dichlorobis(dimethylgloximato)cobalt(IV) 、 potassium carbonate 、 臭氧 、 lithium chloride 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 16.5h， 生成 5-[4-(3-Isopropyl-4-methoxymethoxy-benzyl)-3,5-dimethyl-benzyl]-3-methyl-thiazolidine-2,4-dione
  参考文献：
  名称：

  Design and synthesis of complementing ligands for mutant thyroid hormone receptor TRβ(R320H): a tailor-made approach toward the treatment of resistance to thyroid hormone

  摘要：

  The thyroid hormone receptors (TR) are ligand-dependant transcription factors that regulate key genes involved in metabolic regulation, thermogenesis and development. Resistance to thyroid hormone (RTH) is a genetic disease associated with mutations to TR beta that lack or show reduced responsiveness to thyroid hormone (triiodothyronine). Previously we reported that the neutral alcohol-based thyromimetic HY-1 can selectively restore activity to a functionally impaired form of TR associated with RTH without over-stimulating TR alpha, which has been associated with undesirable side effects. Two new series of tetrazole and thiazolidinedione based ligands were evaluated for their ability to recover potency and efficacy to three of the most common RTH-associated mutants, TR beta(R320C), TR beta(R320H), and TR beta(R316H), in cell based assays. A new thiazolidinedione based ligand AH-9 was identified, which has near wild-type potency (EC50 = 0.54 nM) to TR beta(R320C) and TR beta(R320H). Significantly, AH-9 is equipotent toward TR alpha(wt), TR beta(wt), TR beta(R320C), and TR (RKOH), suggesting that AH-9 may have the potential to restore the normal homeostatic balance of thyroid hormone actions in patients or models harboring these mutations. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.040
• 作为产物：
  描述：

  三氟甲磺酸酐 、 3,5-dimethyl-4-(3'-isopropyl-4'-O-methoxymethylbenzyl)phenol 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到trifluoromethanesulfonic acid 4-(3-isopropyl-4-methoxymethoxybenzyl)-3,5-dimethylphenyl ester
  参考文献：
  名称：

  [EN] NOVEL SULFONIC ACID-CONTAINING THYROMIMETICS, AND METHODS FOR THEIR USE
  [FR] NOUVEAUX THYROMIMETIQUES CONTENANT DE L'ACIDE SULFONIQUE ET METHODES D'UTILISATION ASSOCIEES

  摘要：

  本发明涉及公式IB的含有磺酸基团的化合物，其中G、R1、R3和T如权利要求中所定义，这些化合物与肝脏中的甲状腺受体结合。激活这些受体会导致通过甲状腺激素调节的基因表达的调节。这些化合物可用于治疗包括肥胖、NASH、高胆固醇血症和高脂血症在内的代谢性疾病以及相关疾病和疾患，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。

  公开号：

  WO2010093601A1

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。
• Novel Sulfonic Acid-Containing Thyromimetics, and Methods for Their Use
  申请人：Boyer Serge H.

  公开号：US20120046364A1

  公开（公告）日：2012-02-23

  The present invention relates to sulfonic acid containing compounds of formula IB, in which G, R 1 , R 3 and T are as defined in the claims, 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 obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome X and diabetes.

  本发明涉及公式IB的含有磺酸基团的化合物，其中G、R1、R3和T如权利要求所定义，这些化合物与肝脏中的甲状腺受体结合。激活这些受体会导致调节由甲状腺激素调节的基因表达。这些化合物可用于治疗代谢性疾病和紊乱，包括肥胖症、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、代谢综合症X和糖尿病。