methyl 3-(3-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoate | 1142223-59-3

• 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: methyl 3-(3-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoate
• 英文别名: methyl 3-[3-[[3-tert-butyl-4-(2-fluoro-5-methoxyphenyl)phenyl]methoxy]phenyl]propanoate
• CAS: 1142223-59-3
• 化学式: C₂₈H₃₁FO₄
• 分子量: 450.55
• InChiKey: KRZOSKHQTNJARN-UHFFFAOYSA-N

物化性质

• 沸点：
  549.9±50.0 °C(predicted)
• 密度：
  1.116±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(3-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 15.0h， 以75%的产率得到3-[3-(2-(1,1-dimethyl-ethyl)-2'-fluoro-5'-methoxy-biphenyl-4-ylmethoxy)-phenyl]-propionic acid
  参考文献：
  名称：

  Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist

  摘要：

  GPR40 (FFA1) is a G-protein-coupled receptor, primarily expressed in pancreatic islets, the activation of which elicits increased insulin secretion only in the presence of elevated glucose levels. A potent, orally bioavailable small molecule GPR40 agonist is hypothesized to be an effective antidiabetic posing little or no risk of hypoglycemia. We recently reported the discovery of AMG 837 (1), a potent partial agonist of GPR40. Herein, we present the optimization from the GPR40 partial agonist 1 to the structurally and pharmacologically distinct GPR40 full agonist AM-1638 (21). Moreover, we demonstrate the improved in vivo efficacy that GPR40 full agonist 21 exhibits in BDF/DIO mice as compared to partial agonist 1.

  DOI：

  10.1021/ml300133f
• 作为产物：
  描述：

  3-叔丁基-4-羟基苯甲酸甲酯 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 氯化亚砜 、 potassium carbonate 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.0h， 生成 methyl 3-(3-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoate
  参考文献：
  名称：

  Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist

  摘要：

  GPR40 (FFA1) is a G-protein-coupled receptor, primarily expressed in pancreatic islets, the activation of which elicits increased insulin secretion only in the presence of elevated glucose levels. A potent, orally bioavailable small molecule GPR40 agonist is hypothesized to be an effective antidiabetic posing little or no risk of hypoglycemia. We recently reported the discovery of AMG 837 (1), a potent partial agonist of GPR40. Herein, we present the optimization from the GPR40 partial agonist 1 to the structurally and pharmacologically distinct GPR40 full agonist AM-1638 (21). Moreover, we demonstrate the improved in vivo efficacy that GPR40 full agonist 21 exhibits in BDF/DIO mice as compared to partial agonist 1.

  DOI：

  10.1021/ml300133f

文献信息

• [EN] SUBSTITUTED BIPHENYL GPR40 MODULATORS<br/>[FR] MODULATEURS DU GPR40 À BIPHÉNYLE SUBSTITUÉ
  申请人：AMGEN INC

  公开号：WO2009048527A1

  公开（公告）日：2009-04-16

  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 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.

  本发明提供了一种有用的化合物，例如，用于治疗受试者的代谢紊乱。这些化合物具有一般公式I：其中变量的定义在此处提供。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。
• Substituted biphenyl GPR40 modulators
  申请人：Amgen Inc.

  公开号：US08030354B2

  公开（公告）日：2011-10-04

  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 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.

  本发明提供了一些有用的化合物，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，其中变量的定义在此提供。本发明还提供包括这些化合物的组合物，并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。
• US8030354B2
  申请人：——

  公开号：US8030354B2

  公开（公告）日：2011-10-04
• Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist
  作者：Sean P. Brown、Paul J. Dransfield、Marc Vimolratana、XianYun Jiao、Liusheng Zhu、Vatee Pattaropong、Ying Sun、Jinqian Liu、Jian Luo、Jane Zhang、Simon Wong、Run Zhuang、Qi Guo、Frank Li、Julio C. Medina、Gayathri Swaminath、Daniel C.-H. Lin、Jonathan B. Houze

  DOI：10.1021/ml300133f

  日期：2012.9.13

  GPR40 (FFA1) is a G-protein-coupled receptor, primarily expressed in pancreatic islets, the activation of which elicits increased insulin secretion only in the presence of elevated glucose levels. A potent, orally bioavailable small molecule GPR40 agonist is hypothesized to be an effective antidiabetic posing little or no risk of hypoglycemia. We recently reported the discovery of AMG 837 (1), a potent partial agonist of GPR40. Herein, we present the optimization from the GPR40 partial agonist 1 to the structurally and pharmacologically distinct GPR40 full agonist AM-1638 (21). Moreover, we demonstrate the improved in vivo efficacy that GPR40 full agonist 21 exhibits in BDF/DIO mice as compared to partial agonist 1.