(S)-methyl 3-cyclopropyl-3-(3-((2'-fluoro-5'-methoxy-2-((R)-1-methoxy-2,2-dimethylpropyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)propanoate | 1556954-42-7

• 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: (S)-methyl 3-cyclopropyl-3-(3-((2'-fluoro-5'-methoxy-2-((R)-1-methoxy-2,2-dimethylpropyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)propanoate
• 英文别名: methyl (3S)-3-cyclopropyl-3-[3-[[4-(2-fluoro-5-methoxyphenyl)-3-[(1R)-1-methoxy-2,2-dimethylpropyl]phenyl]methoxy]phenyl]propanoate
• CAS: 1556954-42-7
• 化学式: C₃₃H₃₉FO₅
• 分子量: 534.668
• InChiKey: ILMYXSLGONTWRQ-UCGGBYDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-methyl 3-cyclopropyl-3-(3-((2'-fluoro-5'-methoxy-2-((R)-1-methoxy-2,2-dimethylpropyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)propanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 16.0h， 以72%的产率得到(S)-3-cyclopropyl-3-(3-((2'-fluoro-5'-methoxy-2-((R)-1-methoxy-2,2-dimethylpropyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)propanoic acid
  参考文献：
  名称：

  Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists

  摘要：

  We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.

  DOI：

  10.1021/ml4005123
• 作为产物：
  描述：

  (R)-tert-butyl((2'-fluoro-5'-methoxy-2-(1-methoxy-2,2-dimethylpropyl)-[1,1'-biphenyl]-4-yl)methoxy)dimethylsilane 在 氯化亚砜 、 caesium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (S)-methyl 3-cyclopropyl-3-(3-((2'-fluoro-5'-methoxy-2-((R)-1-methoxy-2,2-dimethylpropyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)propanoate
  参考文献：
  名称：

  Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists

  摘要：

  We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.

  DOI：

  10.1021/ml4005123

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：Brown Sean P.

  公开号：US20090137561A1

  公开（公告）日：2009-05-28

  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式I，其中变量的定义在此提供。本发明还提供包括该化合物的组合物以及使用该化合物制备药物和治疗代谢紊乱（例如2型糖尿病）的方法。
• US8030354B2
  申请人：——

  公开号：US8030354B2

  公开（公告）日：2011-10-04
• Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists
  作者：Xiaohui Du、Paul J. Dransfield、Daniel C.-H. Lin、Simon Wong、Yingcai Wang、Zhongyu Wang、Todd Kohn、Ming Yu、Sean P. Brown、Marc Vimolratana、Liusheng Zhu、An-Rong Li、Yongli Su、Xianyun Jiao、Jiwen (Jim) Liu、Gayathri Swaminath、Thanhvien Tran、Jian Luo、Run Zhuang、Jane Zhang、Qi Guo、Frank Li、Richard Connors、Julio C. Medina、Jonathan B. Houze

  DOI：10.1021/ml4005123

  日期：2014.4.10

  We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.