4-chloro-3'-chloromethyl-2-methyl-biphenyl | 916220-07-0

• 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: 4-chloro-3'-chloromethyl-2-methyl-biphenyl
• 英文别名: 4-chloro-3'-chloromethyl-2-methylbiphenyl；4-chloro-3'-(chloromethyl)-2-methylbiphenyl；4-chloro-1-[3-(chloromethyl)phenyl]-2-methylbenzene
• CAS: 916220-07-0
• 化学式: C₁₄H₁₂Cl₂
• 分子量: 251.155
• InChiKey: CLSKNUFUNUNQLD-UHFFFAOYSA-N

物化性质

• 沸点：
  345.3±32.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  4-chloro-3'-chloromethyl-2-methyl-biphenyl 在 水 、 caesium carbonate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-3-(4-((4'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)hex-4-ynoic acid
  参考文献：
  名称：

  Optimization of GPR40 Agonists for Type 2 Diabetes

  摘要：

  GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as a clinical candidate. Here we report our efforts in searching for structurally distinct back-ups for AMG 837. These efforts led to the identification of more polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent pharmacokinetic properties across species, and minimum central nervous system (CNS) penetration.

  DOI：

  10.1021/ml400501x
• 作为产物：
  描述：

  4-氯-2-甲基苯硼酸 在 lithium aluminium tetrahydride 、 氯化亚砜 、 palladium 10% on activated carbon 、 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 生成 4-chloro-3'-chloromethyl-2-methyl-biphenyl
  参考文献：
  名称：

  Optimization of GPR40 Agonists for Type 2 Diabetes

  摘要：

  GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as a clinical candidate. Here we report our efforts in searching for structurally distinct back-ups for AMG 837. These efforts led to the identification of more polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent pharmacokinetic properties across species, and minimum central nervous system (CNS) penetration.

  DOI：

  10.1021/ml400501x

文献信息

• Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders
  申请人：Houze Jonathan

  公开号：US20060270724A1

  公开（公告）日：2006-11-30

  The present invention provides compounds useful, for example, for modulating insulin levels in a subject, having the general formula I: wherein Q is an optionally substituted phenyl; L is a bond or O; P is a benzene or an optionally substituted thiazole ring; and R 1 has the values provided herein. The present invention also provides compositions, uses, and methods for use of the compounds, for instance, for treatment of type II diabetes.

  本发明提供了一种化合物，例如，用于调节受试者体内胰岛素水平，其具有一般式I： 其中Q是可选择取代的苯基；L是键或O；P是苯环或可选择取代的噻唑环；R1具有此处提供的值。本发明还提供了所述化合物的组合物、用途和使用方法，例如，用于治疗2型糖尿病。
• Bicyclic carboxylic acid derivatives useful for treating metabolic disorders
  申请人：Sharma Rajiv

  公开号：US20070244155A1

  公开（公告）日：2007-10-18

  Compounds having the general formula I and/or the general formula II are useful, for example, for treating metabolic disorders in a subject where the variables are provided herein. Compositions and methods for using the compounds for preparing medicaments and for treating metabolic disorders such as, for instance, type II diabetes are disclosed.

  具有一般式I和/或一般式II的化合物可用于治疗受试者的代谢性疾病，其中变量在此处提供。本文揭示了使用这些化合物制备药物和治疗代谢性疾病（例如2型糖尿病）的组合物和方法。
• 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。