(6-hydroxy-1H-indol-3-yl)acetic acid methyl ester | 116621-16-0

• 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: (6-hydroxy-1H-indol-3-yl)acetic acid methyl ester
• 英文别名: Methyl 2-(6-hydroxy-1H-indol-3-yl)acetate
• CAS: 116621-16-0
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: XUVKTLDUBAQCEN-UHFFFAOYSA-N

物化性质

• 沸点：
  409.8±30.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6-hydroxy-1H-indol-3-yl)acetic acid methyl ester 在 三丁基膦 、 水 、 sodium hydride 、 sodium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 mineral oil 为溶剂， 反应 17.0h， 生成 2-[1-Benzyl-6-(3-carbazol-9-ylpropoxy)indol-3-yl]acetic acid
  参考文献：
  名称：

  Design and synthesis of alkoxyindolyl-3-acetic acid analogs as peroxisome proliferator-activated receptor-γ/δ agonists

  摘要：

  A series of carbazole or phenoxazine containing alkoxyindole-3-acetic acid analogs were prepared as PPAR gamma/delta agonists and their transactivation activities for PPAR receptor subtypes (alpha, gamma and delta) were investigated. Structure-activity relationship studies disclosed the effect of the lipophilic tail, attaching position of the alkoxy group and N-benzyl substitution at indole. Compound 1b was the most potent for PPARd and 3b for PPAR gamma. Molecular modeling suggested two different binding modes of our alkoxyindole-3-acetic acid analogs providing the insight into their PPAR activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.033
• 作为产物：
  描述：

  4-碘-3-硝基苯酚 在 吡啶 、 偶氮二异丁腈 、 三光气 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 三正丁基氢锡 、 palladium diacetate 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 三对苯甲基膦 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 、 丙酮 、 甲苯 、 乙腈 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 11.5h， 生成 (6-hydroxy-1H-indol-3-yl)acetic acid methyl ester
  参考文献：
  名称：

  Design and synthesis of alkoxyindolyl-3-acetic acid analogs as peroxisome proliferator-activated receptor-γ/δ agonists

  摘要：

  A series of carbazole or phenoxazine containing alkoxyindole-3-acetic acid analogs were prepared as PPAR gamma/delta agonists and their transactivation activities for PPAR receptor subtypes (alpha, gamma and delta) were investigated. Structure-activity relationship studies disclosed the effect of the lipophilic tail, attaching position of the alkoxy group and N-benzyl substitution at indole. Compound 1b was the most potent for PPARd and 3b for PPAR gamma. Molecular modeling suggested two different binding modes of our alkoxyindole-3-acetic acid analogs providing the insight into their PPAR activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.033

文献信息

• Identification of a Novel PPAR-γ Agonist through a Scaffold Tuning Approach
  作者：Hyo Gim、Yong-Sung Choi、Hua Li、Yoon-Jung Kim、Jae-Ha Ryu、Raok Jeon

  DOI：10.3390/ijms19103032

  日期：——

  fatty liver disease. Recently, they have been highlighted as attractive targets for the treatment of cardiovascular diseases and chronic myeloid leukemia. The PPAR agonist structure is consists of a polar head, a hydrophobic tail, and a linker. Each part interacts with PPARs through hydrogen bonds or hydrophobic interactions to stabilize target protein conformation, thus increasing its activity. Acidic

  过氧化物酶体增殖物激活受体（PPAR）是包括肥胖症，代谢综合征，糖尿病和非酒精性脂肪肝在内的代谢疾病的重要靶标。最近，它们已被突出为治疗心血管疾病和慢性粒细胞白血病的诱人靶标。PPAR激动剂结构由极性头，疏水尾和连接基组成。每个部分都通过氢键或疏水相互作用与PPAR相互作用，以稳定靶蛋白的构象，从而增加其活性。酸性头对于PPAR激动剂活性至关重要。芳族接头在与PPAR进行疏水相互作用以及调节整个分子的头尾距离和构象方面起着重要作用。通过调整化合物的支架，整个分子可以适合配体结合域以实现适当的结合模式。我们将吲哚-3-基乙酸支架改性为（吲哚-1-基甲基）苯甲酸，而2,4-二氯苯胺固定为疏水尾。我们设计，合成和测定了带有（吲哚-1-基甲基）苯甲酸支架的新型吲哚化合物的体外活性。化合物12是比吡格列酮和我们之前的热门化合物更有效的PPAR-γ激动剂。分子对接研究可能表明化合物12和PPAR-γ之
• Indole derivatives as ppar modulators
  申请人：Conner Eugene Scott

  公开号：US20060166983A1

  公开（公告）日：2006-07-27

  The present invention is directed to a method of treatment by modulating a peroxisome proliferator activated receptor by employing a compound of Structural Formula (I). The variables in (I) are defined herein. Also included are compounds, methods of making compounds, and pharmaceutical compositions. The compounds of the present invention are believed to be effective in treating and preventing Syndrome X, Type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, atherosclerosis, and other disorders related to Syndrome X and cardiovascular diseases.

  本发明涉及一种通过使用结构式(I)的化合物调节过氧化物酶体增殖物激活受体进行治疗的方法。式(I)中的变量在此定义。还包括化合物、制备化合物的方法和制药组合物。本发明的化合物被认为对治疗和预防X综合症、2型糖尿病、高血糖、高脂血症、肥胖症、凝血障碍、高血压、动脉粥样硬化以及其他与X综合症和心血管疾病有关的疾病有效。
• Fused heterocyclic derivates as ppar modulators
  申请人：Conner Eugene Scott

  公开号：US20060217374A1

  公开（公告）日：2006-09-28

  The present invention is directed to a method of treatment by modulating a peroxisome proliferator activated receptor by employing a compound of Structural Formula (I). The variables in I are defined herein. Also included are compounds, methods of making compounds, and pharmaceutical compositions. The compounds of the present invention are believed to be effective in treating and preventing Syndrome X, Type H diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, atherosclerosis, and other disorders related to Syndrome X and cardiovascular diseases.

  本发明涉及一种通过利用结构式（I）的化合物来调节过氧化物酶体增殖物激活受体进行治疗的方法。I中的变量在此定义。还包括化合物、制备化合物的方法和制药组合物。本发明的化合物被认为在治疗和预防综合征X、H型糖尿病、高血糖、高脂血症、肥胖症、凝血障碍、高血压、动脉粥样硬化和其他与综合征X和心血管疾病相关的疾病方面具有疗效。
• Fused heterocyclic derivatives as PPAR modulators
  申请人：Eli Lilly and Company

  公开号：US07528160B2

  公开（公告）日：2009-05-05

  The present invention is directed to a method of treatment by modulating a peroxisome proliferator activated receptor by employing a compound of Structural Formula (I). The variables in I are defined herein. Also included are compounds, methods of making compounds, and pharmaceutical compositions. The compounds of the present invention are believed to be effective in treating and preventing Syndrome X, Type H diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, atherosclerosis, and other disorders related to Syndrome X and cardiovascular diseases.

  本发明涉及一种通过使用结构式（I）化合物调节过氧化物酶体增殖激活受体进行治疗的方法。I中的变量在此定义。还包括化合物、制备化合物的方法和制药组合物。本发明的化合物被认为对治疗和预防综合征X、H型糖尿病、高血糖、高脂血症、肥胖症、凝血异常、高血压、动脉粥样硬化和与综合征X和心血管疾病相关的其他疾病有效。
• Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists
  作者：Hyo Jin Gim、Hua Li、Ji Hye Jeong、Su Jeong Lee、Mi-Kyung Sung、Mi-Young Song、Byung-Hyun Park、Soo Jin Oh、Jae-Ha Ryu、Raok Jeon

  DOI：10.1016/j.bmc.2015.04.046

  日期：2015.7

  A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome proliferator-activated receptor (PPAR) agonists. Structure-activity relationship study indicated that PPAR alpha/gamma/delta activities were dependent on the nature of the hydrophobic group, the attachment position of the alkoxy linker to the indole ring, and N-alkylation of indole nitrogen. Some compounds presented significant PPAR gamma/delta activity and molecular modeling suggested their putative binding modes in the ligand binding domain of PPAR gamma. Of these, compound 51 was selected for in vivo study via an evaluation of microsomal stability in mouse and human liver. Compound 51 lowered the levels of fasting blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When compound 51 was treated, hepatic triglycerides level and the size of adipocytes in white adipose tissue of db/db mice were also reduced as opposed to treatment with rosiglitazone. Taken together, compound 51 shows high potential warranting further studies in models for diabetes and related metabolic disorders and may be in use as a chemical tool for the understanding of PPAR biology. (C) 2015 Elsevier Ltd. All rights reserved.