(1-methyl-1H-imidazol-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone | 916220-01-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1-methyl-1H-imidazol-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone
• 英文别名: (1-methylimidazol-2-yl)-[4-(oxan-2-yloxy)phenyl]methanone
• CAS: 916220-01-4
• 化学式: C₁₆H₁₈N₂O₃
• 分子量: 286.331
• InChiKey: KCQVBWVUGHSHHM-UHFFFAOYSA-N

物化性质

• 沸点：
  496.8±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1-methyl-1H-imidazol-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone 在 palladium 10% on activated carbon 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 异丙醇 为溶剂， 反应 12.0h， 生成 (S)-ethyl 3-(4-hydroxyphenyl)-3-(1-methyl-1H-imidazol-2-yl)propanoate
  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：

  magnesium,2-(phenoxy)oxane,bromide 在 pyridinium dichromate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 (1-methyl-1H-imidazol-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone
  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

• Conformationally constrained 3-(4-hydroxy-phenyl)-substituted-propanoic acids useful for treating metabolic disorders
  申请人：Akerman Michelle

  公开号：US20070066647A1

  公开（公告）日：2007-03-22

  The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables Q, L 1 , L 2 , M, X, L 3 , and A are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.

  本发明提供了一种化合物，例如用于治疗受试者的代谢紊乱。这些化合物具有一般式I： 其中变量Q、L1、L2、M、X、L3和A的定义在此处提供。本发明还提供了包括这些化合物的组合物，以及使用这些化合物制备药物和治疗代谢紊乱的方法，例如II型糖尿病。
• 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。
• Benzo-fused compounds for use in treating metabolic disorders
  申请人：Brown Sean P.

  公开号：US20080119511A1

  公开（公告）日：2008-05-22

  The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables and A are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.

  本发明提供了一些化合物，可用于治疗受试者的代谢紊乱等疾病。这些化合物的一般式为I，其中变量和A的定义在此提供。本发明还提供了包含这些化合物的组合物，以及使用这些化合物制备药物和治疗代谢紊乱（例如2型糖尿病）的方法。
• BENZO-FUSED COMPOUNDS FOR USE IN TREATING METABOLIC DISORDERS
  申请人：Brown Sean P.

  公开号：US20100137323A1

  公开（公告）日：2010-06-03

  The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables Q, L 1 , , L 2 ,M, X, L 3 , and A are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.

  本发明提供了一些化合物，例如用于治疗受试者代谢紊乱的化合物。这些化合物具有一般式I，其中变量Q、L1、L2、M、X、L3和A的定义在本文中提供。本发明还提供了包括这些化合物的组合物，以及使用这些化合物制备药物和治疗代谢紊乱的方法，例如II型糖尿病。
• Optimization of GPR40 Agonists for Type 2 Diabetes
  作者：Jiwen (Jim) Liu、Yingcai Wang、Zhihua Ma、Mike Schmitt、Liusheng Zhu、Sean P. Brown、Paul J. Dransfield、Ying Sun、Rajiv Sharma、Qi Guo、Run Zhuang、Jane Zhang、Jian Luo、George R. Tonn、Simon Wong、Gayathri Swaminath、Julio C. Medina、Daniel C.-H. Lin、Jonathan B. Houze

  DOI：10.1021/ml400501x

  日期：2014.5.8

  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.