2',6'-dimethyl-6-methoxybiphenyl-3-carbaldehyde | 955929-57-4

• 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: 2',6'-dimethyl-6-methoxybiphenyl-3-carbaldehyde
• 英文别名: 6-methoxy-2',6'-dimethylbiphenyl-3-carbaldehyde；3-(2,6-dimethylphenyl)-4-methoxybenzaldehyde
• CAS: 955929-57-4
• 化学式: C₁₆H₁₆O₂
• 分子量: 240.302
• InChiKey: XVYKUVSBTSTVCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2',6'-dimethyl-6-methoxybiphenyl-3-carbaldehyde 在 sodium tetrahydroborate 、 三丁基膦 、 sodium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 甲苯 为溶剂， 生成 {6-[(6-methoxy-2',6'-dimethylbiphenyl-3-yl)methoxy]-2,3-dihydro-1-benzofuran-3-yl}acetic acid
  参考文献：
  名称：

  Identification of Fused-Ring Alkanoic Acids with Improved Pharmacokinetic Profiles that Act as G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonists

  摘要：

  The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to beta-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.

  DOI：

  10.1021/jm2012968
• 作为产物：
  描述：

  2,6-二甲基溴苯 、 5-醛基-2-甲氧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 24.0h， 以87%的产率得到2',6'-dimethyl-6-methoxybiphenyl-3-carbaldehyde
  参考文献：
  名称：

  Identification of Fused-Ring Alkanoic Acids with Improved Pharmacokinetic Profiles that Act as G Protein-Coupled Receptor 40/Free Fatty Acid Receptor 1 Agonists

  摘要：

  The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to beta-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.

  DOI：

  10.1021/jm2012968

文献信息

• Propionic Acid Derivatives and Methods of Use Thereof
  申请人：Biediger Ronald J.

  公开号：US20180312523A1

  公开（公告）日：2018-11-01

  Provided herein are compounds and pharmaceutical compositions of formula I where R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as described herein. Also provided pharmaceutically acceptable salts or stereoisomers of these compounds. In addition methods are provided for inhibiting the binding of an integrin to treat various pathophysiological conditions.

  本文提供了公式I的化合物和药物组合物，其中R1、R2、R3、R4、R5和R6如本文所述。还提供了这些化合物的药用可接受盐或立体异构体。此外，还提供了用于抑制整合素结合以治疗各种病理生理条件的方法。
• Oxadiazolidinedione compound
  申请人：Astellas Pharma Inc.

  公开号：US07968552B2

  公开（公告）日：2011-06-28

  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. 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.

  提供了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/治疗与GPR40相关的疾病，例如糖尿病等。发现一种噁唑烷二酮化合物，其特征在于在噁唑烷二酮环的2位通过连接基与环状基团结合的苄基或类似基团，或其药学上可接受的盐具有优异的GPR40激动剂作用。此外，由于本发明的噁唑烷二酮化合物显示出优异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。
• 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。
• OXADIAZOLIDINEDIONE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP2011788A1

  公开（公告）日：2009-01-07

  [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]本发明提供了一种可用作药物的化合物，特别是胰岛素分泌促进剂或预防/治疗与 GPR40 有关的疾病（如糖尿病或类似疾病）的药物。 [解决方法]研究发现，一种噁二唑烷二酮化合物或其药学上可接受的盐具有优异的 GPR40 激动剂作用，该化合物的特点是在噁二唑烷二酮环的 2 位上通过连接物具有与环基结合的苄基或类似取代基。此外，由于本发明的噁二唑烷二酮化合物具有优异的促进胰岛素分泌作用和降低血糖作用，因此可用作胰岛素分泌促进剂或预防/治疗糖尿病的药物。
• Propionic acid derivatives and methods of use thereof
  申请人：Biediger Ronald J.

  公开号：US10875875B2

  公开（公告）日：2020-12-29

  Provided herein are compounds and pharmaceutical compositions of formula I where R1, R2, R3, R4, R5 and R6 are as described herein. Also provided pharmaceutically acceptable salts or stereoisomers of these compounds. In addition methods are provided for inhibiting the binding of an integrin to treat various pathophysiological conditions.

  本文提供了式 I 的化合物和药物组合物 其中 R1、R2、R3、R4、R5 和 R6 如本文所述。还提供了这些化合物的药学上可接受的盐或立体异构体。此外，还提供了抑制整合素结合以治疗各种病理生理状况的方法。