methyl [(3S)-6-({4'-[2-(ethylsulfanyl)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate | 1000413-88-6

• 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: methyl [(3S)-6-({4'-[2-(ethylsulfanyl)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate
• 英文别名: methyl [(3S)-6-({4'-[2-(ethylthio)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate；methyl[(3S)-6-({4'-[2-(ethylthio)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate；methyl 2-[(3S)-6-[[3-[4-(2-ethylsulfanylethoxy)-2,6-dimethylphenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetate
• CAS: 1000413-88-6
• 化学式: C₃₀H₃₄O₅S
• 分子量: 506.663
• InChiKey: PVYHAHCCQXSTHC-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  79.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl [(3S)-6-({4'-[2-(ethylsulfanyl)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate 在 甲醇 、 sodium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.5h， 以89%的产率得到[(3S)-6-({4'-[2-(ethylsulfanyl)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid
  参考文献：
  名称：

  WO2008/1931

  摘要：

  公开号：
• 作为产物：
  描述：

  2,3-二氢-6-羟基-3-香豆酮乙酸甲酯 在 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 乙醇 、 正己烷 、 甲苯 为溶剂， 反应 20.0h， 生成 methyl [(3S)-6-({4'-[2-(ethylsulfanyl)ethoxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate
  参考文献：
  名称：

  Optimization of (2,3-Dihydro-1-benzofuran-3-yl)acetic Acids: Discovery of a Non-Free Fatty Acid-Like, Highly Bioavailable G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonist as a Glucose-Dependent Insulinotropic Agent

  摘要：

  G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic beta-cells. We previously identified (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase-3/7 activity at 30 mu M (a marker of toxicity in human HepG2 hepatocytes). Three optimized compounds showed promising pharmacokinetic profiles with good in vivo effects. Of these, compound 16 had the lowest lipophilicity. Metabolic analysis of 16 showed a long-acting PK profile due to high resistance to beta-oxidation. Oral administration of 16 significantly reduced plasma glucose excursion and increased insulin secretion during an OGTT in type 2 diabetic rats. Compound 16 (TAK-875) is being evaluated in human clinical trials for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm300170m

文献信息

• FUSED CYCLIC COMPOUNDS
  申请人：Yasuma Tsuneo

  公开号：US20100004312A1

  公开（公告）日：2010-01-07

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明提供一种化合物，其表示为公式（I）：其中每个符号如描述中所定义，或其盐。该化合物或其盐或其前药具有GPR40受体功能调节作用，并可用作胰岛素分泌剂或用于预防或治疗糖尿病等药物。
• Fused cyclic compounds
  申请人：Yasuma Tsuneo

  公开号：US20100197761A1

  公开（公告）日：2010-08-05

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明提供一种化合物，其化学式表示为（I）：其中每个符号如描述中所定义，或其盐。该化合物或其盐或其前药具有GPR40受体功能调节作用，并且可用作胰岛素分泌剂或预防或治疗糖尿病等疾病的药物。
• WO2008/1931
  申请人：——

  公开号：——

  公开（公告）日：——
• US7732626B2
  申请人：——

  公开号：US7732626B2

  公开（公告）日：2010-06-08
• US8088821B2
  申请人：——

  公开号：US8088821B2

  公开（公告）日：2012-01-03