(R)-methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate | 1142223-06-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate
• 英文别名: methyl (3R)-3-cyclopropyl-3-(3-hydroxyphenyl)propanoate
• CAS: 1142223-06-0
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: PXBFBXFVUPMAJK-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate 、 [2-(2-azido-1,1-dimethyl-ethoxy)-2'-fluoro-5'-methoxy-biphenyl-4-yl]methanol 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 以35 %的产率得到(R)-3-{3-[2-(2-azido-1,1-dimethyl-ethoxy)-2'-fluoro-5'-methoxy-biphenyl-4-ylmethoxy]phenyl}-3-cyclopropyl-propionic acid methyl ester
  参考文献：
  名称：

  [EN] ANTIDIABETIC COMPOUNDS AND COMPOSITIONS
  [FR] COMPOSES ANTIDIABÉTIQUES ET COMPOSITIONS

  摘要：

  Provided herein are novel compounds (e.g., Formula I, II, II-B, III, or III-B), pharmaceutical compositions, and methods of using related to GPR40. The compounds herein are typically GPR40 agonists, which can be used for treating a variety of disorders, conditions or diseases such as Type 2 diabetes.

  公开号：

  WO2023134712A1
• 作为产物：
  描述：

  间羟基苯甲醛 在 硫酸 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 (R)-methyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate
  参考文献：
  名称：

  [EN] ANTIDIABETIC COMPOUNDS AND COMPOSITIONS
  [FR] COMPOSES ANTIDIABÉTIQUES ET COMPOSITIONS

  摘要：

  Provided herein are novel compounds (e.g., Formula I, II, II-B, III, or III-B), pharmaceutical compositions, and methods of using related to GPR40. The compounds herein are typically GPR40 agonists, which can be used for treating a variety of disorders, conditions or diseases such as Type 2 diabetes.

  公开号：

  WO2023134712A1

文献信息

• [EN] ANTIDIABETIC BICYCLIC COMPOUNDS<br/>[FR] COMPOSÉS BICYCLIQUES ANTIDIABÉTIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2014130608A1

  公开（公告）日：2014-08-28

  Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  结构式（I）的新型化合物及其药用盐是G蛋白偶联受体40（GPR40）的激动剂，可能在治疗、预防和抑制由G蛋白偶联受体40介导的疾病方面具有用处。本发明的化合物可能在治疗2型糖尿病以及与该疾病常相关的病症方面有用，包括肥胖和脂质紊乱，如混合性或糖尿病性脂质代谢异常、高脂血症、高胆固醇血症和高甘油三酯血症。
• Design and Synthesis of Novel, Selective GPR40 AgoPAMs
  作者：Christopher W. Plummer、Matthew J. Clements、Helen Chen、Murali Rajagopalan、Hubert Josien、William K. Hagmann、Michael Miller、Maria E. Trujillo、Melissa Kirkland、Daniel Kosinski、Joel Mane、Michele Pachanski、Boonlert Cheewatrakoolpong、Andrew F. Nolting、Robert Orr、Melodie Christensen、Louis-Charles Campeau、Michael J. Wright、Randal Bugianesi、Sarah Souza、Xiaoping Zhang、Jerry Di Salvo、Adam B. Weinglass、Richard Tschirret-Guth、Ravi Nargund、Andrew D. Howard、Steven L. Colletti

  DOI：10.1021/acsmedchemlett.6b00443

  日期：2017.2.9

  hypoglycemia. GPR40 agoPAMs have shown superior efficacy to partial agonists as assessed in a glucose tolerability test (GTT). Herein, we report the discovery and optimization of a series of potent, selective GPR40 agoPAMs. Compound 24 demonstrated sustained glucose lowering in a chronic study of Goto Kakizaki rats, showing no signs of tachyphylaxis for this mechanism.

  GPR40是一种主要在胰岛和肠道L细胞中表达的G蛋白偶联受体，已经成为II型糖尿病的重要近期治疗靶标。仅当血糖水平升高时，部分激动剂激活GPR40才能引发胰岛素分泌，从而将低血糖症的风险降至最低。GPR40 agoPAMs在糖耐量测试（GTT）中显示出优于部分激动剂的功效。在此，我们报告了一系列有效的选择性GPR40 agoPAM的发现和优化。在Goto Kakizaki大鼠的一项长期研究中，化合物24显示了持续的葡萄糖降低，对于该机制没有速激肽的迹象。
• [EN] ANTIDIABETIC COMPOUNDS AND COMPOSITIONS<br/>[FR] COMPOSÉS ET COMPOSITIONS ANTIDIABÉTIQUES
  申请人：REZUBIO PHARMACEUTICALS CO LTD

  公开号：WO2022028317A1

  公开（公告）日：2022-02-10

  Provided herein are novel compounds (e.g., Formula I), pharmaceutical compositions, and methods of using related to GPR40. The compounds herein are typically GPR40 agonists, which can be used for treating a variety of disorders, conditions or diseases such as Type 2 diabetes.

  本文提供了新颖的化合物（例如，公式I），药物组合物和与GPR40相关的使用方法。这些化合物通常是GPR40激动剂，可用于治疗各种疾病、疾病或疾病，如2型糖尿病。
• [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。
• ANTIDIABETIC BICYCLIC COMPOUNDS
  申请人：BROCKUNIER Linda L.

  公开号：US20160002255A1

  公开（公告）日：2016-01-07

  Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  结构式（I）的新化合物及其药学上可接受的盐是G蛋白偶联受体40 (GPR40) 的激动剂，可用于治疗、预防和抑制由G蛋白偶联受体40介导的疾病。本发明的化合物可用于治疗2型糖尿病，以及与该疾病常见相关的疾病，包括肥胖和脂质紊乱，如混合型或糖尿病性脂质代谢异常、高脂血症、高胆固醇血症和高三酰甘油血症。