4-(2,4-bis(trifluoromethyl)phenoxy)-3-methoxybenzaldehyde | 1262328-74-4

• 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: 4-(2,4-bis(trifluoromethyl)phenoxy)-3-methoxybenzaldehyde
• 英文别名: 4-[2,4-bis(trifluoromethyl)phenoxy]-3-methoxybenzaldehyde
• CAS: 1262328-74-4
• 化学式: C₁₆H₁₀F₆O₃
• 分子量: 364.244
• InChiKey: BEHZMDOOHMVQPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  340.4±42.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,4-噻唑烷二酮 、 4-(2,4-bis(trifluoromethyl)phenoxy)-3-methoxybenzaldehyde 在 ammonium acetate 、 溶剂黄146 作用下， 以72%的产率得到5-[4-(2,4-bistrifluoromethylphenoxy)-3-methoxybenzylidene]-thiazolidine-2,4-dione
  参考文献：
  名称：

  Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents

  摘要：

  Estrogen-related receptor a (ERR alpha) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of diaryl ether based thiazolidenediones, which function as selective ligands against this receptor. Series optimization provided several potent analogues that inhibit the recruitment of a coactivator peptide fragment in in vitro biochemical assays (IC50 < 150 nM) and cellular two-hybrid reporter assays against the ligand binding domain (IC50 = 1-5 mu M). A cocrystal structure of the ligand-binding domain of ERR alpha with lead compound 29 revealed the presence of a covalent interaction between the protein and ligand, which has been shown to be reversible. In diet-induced murine models of obesity and in an overt diabetic rat model, oral administration of 29 normalized insulin and circulating triglyceride levels, improved insulin sensitivity, and was body weight neutral. This provides the first demonstration of functional activities of an ERRa ligand in metabolic animal models.

  DOI：

  10.1021/jm101063h
• 作为产物：
  描述：

  2,4-双(三氟甲基)氟苯 、 香草醛 在 lithium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以81%的产率得到4-(2,4-bis(trifluoromethyl)phenoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  EP2450352

  摘要：

  公开号：

文献信息

• PROPHYLACTIC OR THERAPEUTIC AGENT FOR CANCER
  申请人：Hasuoka Atsushi

  公开号：US20120196864A1

  公开（公告）日：2012-08-02

  A compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof has a superior activity as an estrogen-related receptor-α modulator, and is useful as a prophylactic or therapeutic agent for cancer.

  化合物的化学式为（I）：其中每个符号如规范中所述，或其盐具有优越的活性作为雌激素相关受体-α调节剂，并且可用作预防或治疗癌症的药物。
• [EN] PROPHYLACTIC OR THERAPEUTIC AGENT FOR CANCER<br/>[FR] AGENT PROPHYLACTIQUE OU THÉRAPEUTIQUE POUR LE CANCER
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2011016501A1

  公开（公告）日：2011-02-10

  　式（Ｉ）：［式中の各記号は、明細書に記載の通りである。］で表される化合物またはその塩は、エストロゲン関連受容体アルファモジュレーターとして優れた活性を有し、癌の予防または治療剤として有用である。
• EP2450352
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents
  作者：Raymond J. Patch、Lily L. Searle、Alexander J. Kim、Debyendu De、Xizhen Zhu、Hossein B. Askari、John C. O’Neill、Marta C. Abad、Dionisios Rentzeperis、Jianying Liu、Michael Kemmerer、Ling Lin、Jyotsna Kasturi、John G. Geisler、James M. Lenhard、Mark R. Player、Micheal D. Gaul

  DOI：10.1021/jm101063h

  日期：2011.2.10

  Estrogen-related receptor a (ERR alpha) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of diaryl ether based thiazolidenediones, which function as selective ligands against this receptor. Series optimization provided several potent analogues that inhibit the recruitment of a coactivator peptide fragment in in vitro biochemical assays (IC50 < 150 nM) and cellular two-hybrid reporter assays against the ligand binding domain (IC50 = 1-5 mu M). A cocrystal structure of the ligand-binding domain of ERR alpha with lead compound 29 revealed the presence of a covalent interaction between the protein and ligand, which has been shown to be reversible. In diet-induced murine models of obesity and in an overt diabetic rat model, oral administration of 29 normalized insulin and circulating triglyceride levels, improved insulin sensitivity, and was body weight neutral. This provides the first demonstration of functional activities of an ERRa ligand in metabolic animal models.