4-(3-isopropyl-4-(methoxymethoxy)benzyl)-3,5-dimethylbenzaldehyde | 853201-45-3

• 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: 4-(3-isopropyl-4-(methoxymethoxy)benzyl)-3,5-dimethylbenzaldehyde
• 英文别名: 3,5-dimethyl-4-(3'-isopropyl-4'-methoxymethoxy-benzyl)benzaldehyde；3,5-Dimethyl-4-(3'-isopropyl-4'-methoxymethoxybenzyl)-benzaldehyde；4-[[4-(methoxymethoxy)-3-propan-2-ylphenyl]methyl]-3,5-dimethylbenzaldehyde
• CAS: 853201-45-3
• 化学式: C₂₁H₂₆O₃
• 分子量: 326.436
• InChiKey: GNBSABOVDUBUQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-isopropyl-4-(methoxymethoxy)benzyl)-3,5-dimethylbenzaldehyde 在 盐酸 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 60.0h， 生成 methyl 2-[4-(4-hydroxy-3-isopropylbenzyl)-3,5-dimethylphenyl]-2-hydroxyacetate
  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：

  trifluoromethanesulfonic acid 4-(3-isopropyl-4-methoxymethoxybenzyl)-3,5-dimethylphenyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 臭氧 、 lithium chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 4-(3-isopropyl-4-(methoxymethoxy)benzyl)-3,5-dimethylbenzaldehyde
  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

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
• [EN] NOVEL PHOSPHINIC ACID-CONTAINING THYROMIMETICS<br/>[FR] NOUVELLES SUBSTANCES THYROMIMETIQUES CONTENANT DE L'ACIDE PHOSPHINIQUE
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2006128056A2

  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.
• 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
  作者：Atsushi Hashimoto、Youheng Shi、Katherine Drake、John T Koh

  DOI：10.1016/j.bmc.2005.03.040

  日期：2005.6

  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.