N-[1-(4-hydroxy-3-isopropylbenzyl)-7-methyl-1H-indol-4-yl]malonic acid | 1000603-16-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[1-(4-hydroxy-3-isopropylbenzyl)-7-methyl-1H-indol-4-yl]malonic acid
• 英文别名: SKL-13784；N-[1-(4-hydroxy-3-isopropylbenzyl)-7-methyl-1H-indol-4-yl]malonamic acid；3-[[1-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-7-methylindol-4-yl]amino]-3-oxopropanoic acid
• CAS: 1000603-16-6
• 化学式: C₂₂H₂₄N₂O₄
• 分子量: 380.444
• InChiKey: XSZSWHNJVRGLOK-UHFFFAOYSA-N

物化性质

• 沸点：
  687.3±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  91.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[1-(4-hydroxy-3-isopropylbenzyl)-7-methyl-1H-indol-4-yl]malonic acid 、 calcium chloride 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.17h， 生成 calcium N-[1-(4-hydroxy-3-isopropylbenzyl)-7-methyl-1H-indol-4-yl]malonamate
  参考文献：
  名称：

  NOVEL 6-5 BICYCIC HETEROCYCLIC DERIVATIVE AND MEDICAL USE THEREOF

  摘要：

  本发明的目的是提供一种药物，作为甲状腺激素受体配体，其在药物疗效和安全性上足够，并且具有作为药物的优秀作用。本发明提供了一种由以下通式（I）表示的化合物或其药用可接受的盐：[其中[化学公式2]是单键或双键；A是-CH2-或-CO-；X、Y和Z各自独立为氮原子或碳原子；R1是氢原子或芳烷基团；R2是烷基团或芳烷基团等；R3是氢原子或烷基团等；R4是氢原子或烷基团；R5是氢原子、烷基团或卤素低烷基团等；R6是氢原子或烷基团；R7是氢原子等；R8是氢原子或烷基团等；E是-NHCO-G-COR12等（其中G是单键或亚烷基团，R12是羟基或烷氧基）]。

  公开号：

  EP2036887A1
• 作为产物：
  描述：

  4-溴-2-异丙基苯酚 在 咪唑 、 正丁基锂 、 氯化亚砜 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 、 正戊烷 为溶剂， 反应 41.0h， 生成 N-[1-(4-hydroxy-3-isopropylbenzyl)-7-methyl-1H-indol-4-yl]malonic acid
  参考文献：
  名称：

  Synthesis and pharmacological characterization of 1-benzyl-4-aminoindole-based thyroid hormone receptor β agonists

  摘要：

  A series of 1-benzylindole-based TR beta agonists were prepared and evaluated. Compounds 11b' and 11c' were found to have cholesterol-lowering in a rat model with marginal effects on cardiac function and HPT axis. The present work illustrates the potential use of indoles as inner ring isosteres. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.001

文献信息

• NOVEL 6-5 SYSTEM BICYCLIC HETEROCYCLIC DERIVATIVE AND ITS PHARMACEUTICAL UTILITY
  申请人：Asano Yukiyasu

  公开号：US20090176841A1

  公开（公告）日：2009-07-09

  An object of the present invention is to provide a medicament as a thyroid hormone receptor ligand which is sufficient in drug efficacy and safety, and has the excellent action as a drug. The present invention provides a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: [wherein [Chemical Formula 2] is a single bond or a double bond; A is —CH 2 — or —CO—; X, Y, and Z are each independently a nitrogen atom or a carbon atom; R 1 is a hydrogen atom or an aralkyl group; R 2 is an alkyl group or an aralkyl group, etc.; R 3 is a hydrogen atom or an alkyl group, etc.; R 4 is a hydrogen atom or an alkyl group; R 5 is a hydrogen atom, an alkyl group or a halo lower alkyl group, etc.; R 6 is a hydrogen atom or an alkyl group; R 7 is a hydrogen atom, etc.; R 8 is a hydrogen atom, or an alkyl group, etc.; and E is —NHCO-G-COR 12 , etc. (wherein G is a single bond or an alkylene group, and R 12 is a hydroxy group or an alkoxy group)].

  本发明的目的是提供一种作为甲状腺激素受体配体的药物，具有充分的药效和安全性，并具有优秀的药物作用。本发明提供了以下通式（I）所表示的化合物或其药学上可接受的盐：[其中[化学式2]是单键或双键；A是-CH2-或-CO-；X、Y和Z分别是氮原子或碳原子；R1是氢原子或芳基烷基；R2是烷基或芳基烷基等；R3是氢原子或烷基等；R4是氢原子或烷基；R5是氢原子、烷基或卤代低烷基等；R6是氢原子或烷基；R7是氢原子等；R8是氢原子或烷基等；E是-NHCO-G-COR12等（其中G是单键或烷基亚基，R12是羟基或烷氧基）]。
• COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIVER DISORDERS
  申请人：Viking Therapeutics, Inc.

  公开号：US20220016136A1

  公开（公告）日：2022-01-20

  The present disclosure is directed toward the use of thyroid receptor agonists of pharmaceutically acceptable salts thereof, in combination with a second pharmaceutical agent for preventing, treating, or ameliorating fatty liver diseases such as steatosis, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis.
• COMPOSITIONS FOR THE TREATMENT OF FIBROSIS AND INFLAMMATION
  申请人：Viking Therapeutics, Inc.

  公开号：US20220016137A1

  公开（公告）日：2022-01-20

  The present disclosure is directed to methods of treating fibrotic conditions and inflammation by administration of TRβ agonists. The disclosure provides methods wherein the abnormal deposition of extracellular matrix components, such as collagen, keratin, or elastin, is reduced, either through interaction of TRβ agonists with TGF-β-dependent inflammatory pathways, or by other mechanisms, thereby ameliorating fibrotic symptoms.
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIVER DISORDERS<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT DE TROUBLES HÉPATIQUES
  申请人：VIKING THERAPEUTICS INC

  公开号：WO2020117987A1

  公开（公告）日：2020-06-11

  The present disclosure is directed toward the use of thyroid receptor agonists of pharmaceutically acceptable salts thereof, in combination with a second pharmaceutical agent for preventing, treating, or ameliorating fatty liver diseases such as steatosis, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis.
• [EN] COMPOSITIONS FOR THE TREATMENT OF FIBROSIS AND INFLAMMATION<br/>[FR] COMPOSITIONS POUR LE TRAITEMENT DE LA FIBROSE ET DE L'INFLAMMATION
  申请人：VIKING THERAPEUTICS INC

  公开号：WO2020117962A1

  公开（公告）日：2020-06-11

  The present disclosure is directed to methods of treating fibrotic conditions and inflammation by administration of TRβ agonists. The disclosure provides methods wherein the abnormal deposition of extracellular matrix components, such as collagen, keratin, or elastin, is reduced, either through interaction of TRβ agonists with TGF-β–dependent inflammatory pathways, or by other mechanisms, thereby ameliorating fibrotic symptoms.