(5-{3-[3-(4-trifluoromethylbenzyloxy)phenoxy]propoxy}-1H-indol-3-yl)acetic acid

• 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: (5-{3-[3-(4-trifluoromethylbenzyloxy)phenoxy]propoxy}-1H-indol-3-yl)acetic acid
• 英文别名: 2-[5-[3-[3-[[4-(trifluoromethyl)phenyl]methoxy]phenoxy]propoxy]-1H-indol-3-yl]acetic acid
• 化学式: C₂₇H₂₄F₃NO₅
• 分子量: 499.486
• InChiKey: ANAGYBJWYVWOKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  80.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(5-羟基-1H-吲哚-3-基)乙酸甲酯 在 水 、 caesium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 (5-{3-[3-(4-trifluoromethylbenzyloxy)phenoxy]propoxy}-1H-indol-3-yl)acetic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2015.04.046

文献信息

• 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.