methyl (3S)-4,4,4-trifluoro-3-(3-hydroxyphenyl)butanoate | 1142223-00-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: methyl (3S)-4,4,4-trifluoro-3-(3-hydroxyphenyl)butanoate
• CAS: 1142223-00-4
• 化学式: C₁₁H₁₁F₃O₃
• 分子量: 248.202
• InChiKey: BVGRPNSBTLTLHA-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(三氟甲氧基)苯乙酮 在 aluminum (III) chloride 、 10% Pd/C 、 氢气 、 1,2-乙二硫醇 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium chloride 作用下， 以 顺-1,2-二氯乙烯 、 甲醇 、 乙酸乙酯 、 乙腈 为溶剂， 反应 4.0h， 生成 methyl (3R)-4,4,4-trifluoro-3-(3-hydroxyphenyl)butanoate 、 methyl (3S)-4,4,4-trifluoro-3-(3-hydroxyphenyl)butanoate
  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：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
• 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.