ethyl 3-(2-methyl-3,5-difluoro-4-hydroxyphenyl)propanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: ethyl 3-(2-methyl-3,5-difluoro-4-hydroxyphenyl)propanoate
• 英文别名: Ethyl 3-(3,5-difluoro-4-hydroxy-2-methylphenyl)propanoate；ethyl 3-(3,5-difluoro-4-hydroxy-2-methylphenyl)propanoate
• 化学式: C₁₂H₁₄F₂O₃
• 分子量: 244.238
• InChiKey: UAVYNKABYZODMN-UHFFFAOYSA-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：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methyl methanesulfonate 、 ethyl 3-(2-methyl-3,5-difluoro-4-hydroxyphenyl)propanoate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-((3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl)methoxy)-3,5-difluoro-2-methylphenyl)propanoic acid ethyl ester
  参考文献：
  名称：

  Discovery of an Isothiazole-Based Phenylpropanoic Acid GPR120 Agonist as a Development Candidate for Type 2 Diabetes

  摘要：

  We have discovered a novel series of isothiazole-based phenylpropanoic acids as GPR120 agonists. Extensive structure activity relationship studies led to the discovery of a potent GPR120 agonist 4x, which displayed good EC50 values in both calcium and beta-arrestin assays. It also presented good pharmaceutical properties and a favorable PK profile. Moreover, it demonstrated in vivo antidiabetic activity in C57BL/6 DIO mice. Studies in WT and knockout DIO mice showed that it improved glucose handling during an OGTT via GPR120. Overall, 4x possessed promising antidiabetic effect and good safety profile to be a development candidate.

  DOI：

  10.1021/acsmedchemlett.7b00233

文献信息

• [EN] ISOTHIAZOLE DERIVATIVES AS GPR120 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES<br/>[FR] DÉRIVÉS ISOTHIAZOLE UTILES EN TANT QU'AGONISTES DE GPR120 POUR LE TRAITEMENT DU DIABÈTE DE TYPE II
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2015134039A1

  公开（公告）日：2015-09-11

  Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR120 receptor. Such compounds are represented by Formula (I) as follows: wherein R1, G, and Q are defined herein.

  揭示了一种通过调节GPR120受体而影响的疾病的化合物、组合物和治疗方法。这些化合物由以下式（I）表示：其中R1、G和Q在此处定义。
• GPR120 agonists for the treatment of type II diabetes
  申请人：Janssen Pharmaceutica NV

  公开号：US10118922B2

  公开（公告）日：2018-11-06

  Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR120 receptor. Such compounds are represented by Formula (I) and Formula (II) as follows: wherein Y, R1, G, and Q are defined herein; and wherein R11, R21, R41, RB1 and G1, are defined herein.

  公开了用于治疗受 GPR120 受体调节影响的疾病的化合物、组合物和方法。此类化合物由如下式（I）和式（II）表示： 其中 Y、R1、G 和 Q 在本文中定义； 和 其中 R11、R21、R41、RB1 和 G1 在本文中定义。
• GPR120 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
  申请人：Janssen Pharmaceutica, N.V.

  公开号：EP2970161A1

  公开（公告）日：2016-01-20
• ISOTHIAZOLE DERIVATIVES AS GPR120 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
  申请人：Janssen Pharmaceutica NV

  公开号：EP3114123B1

  公开（公告）日：2018-04-25
• US20140275179A1
  申请人：——

  公开号：US20140275179A1

  公开（公告）日：2014-09-18