[2,6-dimethyl-4-(tetrahydro-2H-thiopyran-4-yloxy)phenyl]boronic acid | 922151-76-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [2,6-dimethyl-4-(tetrahydro-2H-thiopyran-4-yloxy)phenyl]boronic acid
• 英文别名: [2,6-dimethyl-4-(thian-4-yloxy)phenyl]boronic acid
• CAS: 922151-76-6
• 化学式: C₁₃H₁₉BO₃S
• 分子量: 266.169
• InChiKey: AIZVEBMAAIPKEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  75
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [2,6-dimethyl-4-(tetrahydro-2H-thiopyran-4-yloxy)phenyl]boronic acid 在 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 三丁基膦 、 caesium carbonate 、 间氯过氧苯甲酸 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 47.5h， 生成 methyl [(3R)-6-({4'-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy]-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
• 作为产物：
  描述：

  硼酸三异丙酯 在 正丁基锂 、 盐酸 、 水 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 以71%的产率得到[2,6-dimethyl-4-(tetrahydro-2H-thiopyran-4-yloxy)phenyl]boronic acid
  参考文献：
  名称：

  WO2008/1931

  摘要：

  公开号：

文献信息

• [EN] CARBOXYLIC ACID COMPOUNDS IN TREATMENT OF DIABETES MELLITUS<br/>[FR] COMPOSÉS D'ACIDE CARBOXYLIQUE DANS LE TRAITEMENT DU DIABÈTE SUCRÉ
  申请人：FUJIAN HAIXI PHARMACEUTICALS CO LTD

  公开号：WO2015024526A1

  公开（公告）日：2015-02-26

  The invention relates to compounds for increasing GPR40 recetpor activity and application thereof. These compounds include of a compound of Formula (I), pharmaceutically acceptable salts thereof, solvates thereof, isomers thereof, or produgs of the compounds mentioned above, or the mixture of any form above mentioned. The invention also relates to the use of the compounds in manufacturing a medicament for the treatment and/or prevention of diabetes, obesity or for Insulin secretagogue.

  该发明涉及增加GPR40受体活性的化合物及其应用。这些化合物包括公式（I）的化合物，其药学上可接受的盐、溶剂化合物、异构体、上述化合物的前药，或上述任何形式的混合物。该发明还涉及将这些化合物用于制造用于治疗和/或预防糖尿病、肥胖或胰岛素分泌素的药物。
• 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。
• Cyclopropanecarboxylic acid compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08153694B2

  公开（公告）日：2012-04-10

  A compound of the formula (I): wherein each symbol is as defined in the description, a salt thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonist activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.

  公式（I）的化合物：其中每个符号如描述中所定义，其盐和前药，意外地具有优越的GPR40受体激动剂活性和作为药物产品的优越性能，如稳定性等，并且可以是安全有效的药物剂型，用于哺乳动物的GPR40受体相关病理或疾病的预防或治疗。
• Cyclopropanecarboxylic Acid Compound
  申请人：Yasuma Tsuneo

  公开号：US20100144806A1

  公开（公告）日：2010-06-10

  A compound of the formula (I): wherein each symbol is as defined in the description, a salt s thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonist activity and superior properties as pharmaceutical products such as stability and the like, and can be safe and useful pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor-related pathology or diseases in mammals.

  公式（I）的化合物：其中每个符号的定义如描述，其盐和其前药，本发明意外地具有优越的GPR40受体激动剂活性和作为药物产品的优越性能，例如稳定性等，可以作为安全和有用的药物剂量用于哺乳动物的预防或治疗GPR40受体相关病理或疾病。