(2,2’,6’-trimethyl-biphenyl-3-yl)-methanol | 691905-45-0

• 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: (2,2’,6’-trimethyl-biphenyl-3-yl)-methanol
• 英文别名: (2,2',6'-trimethyl-biphenyl-3-yl)-methanol；(2,2',6'-trimethylbiphenyl-3-yl)methanol；[3-(2,6-dimethylphenyl)-2-methylphenyl]methanol
• CAS: 691905-45-0
• 化学式: C₁₆H₁₈O
• 分子量: 226.318
• InChiKey: LCHQKELPMOZWMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2,2’,6’-trimethyl-biphenyl-3-yl)-methanol 在 三溴化磷 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 3-bromomethyl-2,2’,6’-trimethyl-biphenyl
  参考文献：
  名称：

  [EN] ANTIDIABETIC TRICYCLIC COMPOUNDS
  [FR] COMPOSÉS TRICYCLIQUES ANTIDIABÉTIQUES

  摘要：

  具有结构公式(I)的新化合物及其药用可接受的盐，是G蛋白偶联受体40（GPR40）的激动剂，可用于治疗、预防和抑制由G蛋白偶联受体40介导的疾病。本发明的化合物可用于治疗2型糖尿病，以及通常与该疾病相关的状况，包括肥胖和脂质紊乱，如混合型或糖尿病性血脂异常、高脂血症、高胆固醇血症和高甘油三酯血症。

  公开号：

  WO2014019186A1
• 作为产物：
  描述：

  2,6-二甲基苯硼酸 在 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 21.0h， 生成 (2,2’,6’-trimethyl-biphenyl-3-yl)-methanol
  参考文献：
  名称：

  Discovery of Phenylpropanoic Acid Derivatives Containing Polar Functionalities as Potent and Orally Bioavailable G Protein-Coupled Receptor 40 Agonists for the Treatment of Type 2 Diabetes

  摘要：

  As part of a program to identify potent GPR40 agonists with drug-like properties suitable for clinical development, the incorporation of polar substituents was explored with the intention of decreasing the lipophilicity of our recently disclosed phenylpropanoic acid derivative 1. This incorporation would allow us to mitigate the cytotoxicity issues observed with compound 1 and enable us to move away from the multifunctional free fatty acid-like structure. Substitutions on the 2',6'-dimethylbiphenyl ring were initially undertaken, which revealed the feasibility of introducing polar functionalities at the biphenyl 4'-position. Further optimization of this position and the linker led to the discovery of several 4'-alkoxybiphenyl derivatives, which showed potent GPR40 agonist activities with the best balance in terms of improved cytotoxicity profiles and favorable pharmacokinetic properties. Among them, 3-{2-fluoro-4[({4'-[(4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoic acid (35) exhibited a robust plasma glucose-lowering effect and insulinotropic action during an oral glucose tolerance test in rats with impaired glucose tolerance.

  DOI：

  10.1021/jm2016123

文献信息

• CARBOXYLIC ACID COMPOUND
  申请人：Negoro Kenji

  公开号：US20120035196A1

  公开（公告）日：2012-02-09

  [Problem] The present invention has an object to provide a compound having a GPR40 agonistic activity, which is useful as a pharmaceutical composition, an insulin secretion promoter, or an agent for preventing/treating diabetes. [Means for Solution] The present inventors have extensively studied a compound having a GPR40 agonistic activity, and as a result, they have found that the compound (I) of the present invention or a pharmaceutically acceptable salt thereof, in which a carboxylic acid is bonded to a bicyclic or tricyclic moiety through methylene, and further, a benzene ring substituted with a monocyclic 6-membered aromatic ring is bonded to a bicyclic or tricyclic moiety through —O-methylene or —NH-methylene, has an excellent GPR40 agonistic activity. They have also found that the compound has an excellent insulin secretion promoting action and strongly inhibits increase in the blood glucose after glucose loading, thereby completing the present invention.

  本发明的目的是提供一种具有GPR40激动活性的化合物，可用作药物组合物、胰岛素分泌促进剂或预防/治疗糖尿病的药物。本发明的发明人广泛研究了具有GPR40激动活性的化合物，结果发现，本发明的化合物(I)或其药学上可接受的盐具有卓越的GPR40激动活性，其中羧酸通过亚甲基与双环或三环部分结合，并且苯环通过—O-亚甲基或—NH-亚甲基与单环6-成员芳香环结合到双环或三环部分。他们还发现该化合物具有卓越的胰岛素分泌促进作用，并强烈抑制葡萄糖负荷后血糖的增加，从而完成了本发明。
• Receptor Function Regulator
  申请人：Fukatsu Kohji

  公开号：US20090012093A1

  公开（公告）日：2009-01-08

  The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明的GPR40受体功能调节剂包括具有芳香环和能够释放阳离子的基团的化合物，可用作胰岛素分泌剂或预防或治疗糖尿病等疾病的药剂。
• ANTIDIABETIC TRICYCLIC COMPOUNDS
  申请人：Liang Gui-Bai

  公开号：US20100216694A1

  公开（公告）日：2010-08-26

  Tricyclic compounds containing a cyclopropanecarboxylic acid fused to a bicyclic ring, including pharmaceutically acceptable salts, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  含有环丙烷羧酸融合到双环环中的三环化合物，包括药学上可接受的盐，是G蛋白偶联受体40（GPR40）的激动剂，是治疗化合物的有用选择，特别是在治疗2型糖尿病和与该疾病常相关的病症方面，包括肥胖和脂质紊乱，如混合型或糖尿病性脂质代谢异常、高脂血症、高胆固醇血症和高三酰甘油血症。
• Antidiabetic tricyclic compounds
  申请人：Liang Gui-Bai

  公开号：US08399507B2

  公开（公告）日：2013-03-19

  Tricyclic compounds containing a cyclopropanecarboxylic acid fused to a bicyclic ring, including pharmaceutically acceptable salts, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  含有环丙烷羧酸融合到双环环的三环化合物，包括药物可接受的盐，是G蛋白偶联受体40(GPR40)的激动剂，可用作治疗化合物，特别是在治疗2型糖尿病以及与该疾病经常相关的病症，包括肥胖和脂质紊乱，如混合或糖尿病性脂质代谢异常、高脂血症、高胆固醇血症和高甘油三酯血症方面有用。
• Oxadiazolidinedione Compound
  申请人：Negoro Kenji

  公开号：US20090186909A1

  公开（公告）日：2009-07-23

  [Problem] A compound which can be used as a pharmaceutical, particularly a insulin secretion promoter or a agent for preventing/treating disease in which GPR40 is concerned such as diabetes or the like, is provided. [Means for resolution] It was found that an oxadiazolidinedione compound which is characterized by the possession of a benzyl or the like substituent binding to the cyclic group via a linker at the 2-position of the oxadiazolidinedione ring, or a pharmaceutically acceptable salt thereof, has excellent GPR40 agonist action. In addition, since the oxadiazolidinedione compound of the present invention showed excellent insulin secretion promoting action and blood glucose level-lowering action, it is useful as an insulin secretion promoter or an agent for preventing/treating diabetes.

  【问题】提供一种可用作药物的化合物，特别是胰岛素分泌促进剂或用于预防/治疗涉及GPR40的疾病，如糖尿病等。 【解决方法】发现一种氧代唑烷二酮化合物，其特征在于在氧代唑烷二酮环的2位通过连接基与环上的苯甲基或类似取代基结合，或其药学上可接受的盐具有优异的GPR40激动剂作用。此外，由于本发明的氧代唑烷二酮化合物表现出良好的胰岛素分泌促进作用和降低血糖水平的作用，因此它可用作胰岛素分泌促进剂或预防/治疗糖尿病的药物。