2-(3-(2-chloro-5-(trifluoromethoxy)phenyl)-7-methyl-3-azaspiro[5.5]undecan-9-yl)acetic acid | 1599478-74-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(3-(2-chloro-5-(trifluoromethoxy)phenyl)-7-methyl-3-azaspiro[5.5]undecan-9-yl)acetic acid
• 英文别名: 2-[3-[2-Chloro-5-(trifluoromethoxy)phenyl]-11-methyl-3-azaspiro[5.5]undecan-9-yl]acetic acid；2-[3-[2-chloro-5-(trifluoromethoxy)phenyl]-11-methyl-3-azaspiro[5.5]undecan-9-yl]acetic acid
• CAS: 1599478-74-6
• 化学式: C₂₀H₂₅ClF₃NO₃
• 分子量: 419.872
• InChiKey: YXMYUZGNDIAWAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-甲酰基-N-CBZ 哌啶 在 copper(l) iodide 、 20% palladium hydroxide-activated charcoal 、 氢气 、 sodium hydride 、 caesium carbonate 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 6.83h， 生成 2-(3-(2-chloro-5-(trifluoromethoxy)phenyl)-7-methyl-3-azaspiro[5.5]undecan-9-yl)acetic acid
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel and Selective G-protein Coupled Receptor 120 (GPR120) Spirocyclic Agonists

  摘要：

  Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14. Furthermore, compound 14 was evaluated in vivo and demonstrated acute glucose lowering in an oral glucose tolerance test (oGTT), as well as improvements in homeostatic measurement assessment of insulin resistance (HOMA-IR; a surrogate marker for insulin sensitization) and an increase in glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp in diet-induced obese (DIO) mice.

  DOI：

  10.1021/acsmedchemlett.6b00360

文献信息

• SUBSTITUTED SPIROPIPERIDINYL COMPOUNDS USEFUL AS GPR120 AGONISTS
  申请人：CHELLIAH Mariappan

  公开号：US20150274672A1

  公开（公告）日：2015-10-01

  The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.

  本发明涉及一种由公式(I)表示的化合物及其药学上可接受的盐，用于治疗或预防糖尿病、高脂血症、肥胖症、与炎症相关的疾病和相关疾病和状况。该化合物是G蛋白偶联受体GPR120的激动剂，是有用的。还包括药物组成物和治疗方法。
• US9708270B2
  申请人：——

  公开号：US9708270B2

  公开（公告）日：2017-07-18
• [EN] SUBSTITUTED SPIROPIPERIDINYL COMPOUNDS USEFUL AS GPR120 AGONISTS<br/>[FR] COMPOSÉS SPIROPIPÉRIDINYLIQUES SUBSTITUÉS UTILES COMME AGONISTES DE GPR120
  申请人：MERCK SHARP & DOHME

  公开号：WO2014059232A2

  公开（公告）日：2014-04-17

  The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.
• Design, Synthesis, and Evaluation of Novel and Selective G-protein Coupled Receptor 120 (GPR120) Spirocyclic Agonists
  作者：Jason M. Cox、Hong D. Chu、Mariappan V. Chelliah、John S. Debenham、Keith Eagen、Ping Lan、Matthew Lombardo、Clare London、Michael A. Plotkin、Unmesh Shah、Zhongxiang Sun、Henry M. Vaccaro、Srikanth Venkatraman、Takao Suzuki、Nengxue Wang、Eric R. Ashley、Alejandro Crespo、Maria Madeira、Dennis H. Leung、Candice Alleyne、Aimie M. Ogawa、Sarah Souza、Brande Thomas-Fowlkes、Jerry Di Salvo、Adam Weinglass、Melissa Kirkland、Michele Pachanski、Mary Ann Powles、Effie Tozzo、Taro E. Akiyama、Feroze Ujjainwalla、James R. Tata、Christopher J. Sinz

  DOI：10.1021/acsmedchemlett.6b00360

  日期：2017.1.12

  Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14. Furthermore, compound 14 was evaluated in vivo and demonstrated acute glucose lowering in an oral glucose tolerance test (oGTT), as well as improvements in homeostatic measurement assessment of insulin resistance (HOMA-IR; a surrogate marker for insulin sensitization) and an increase in glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp in diet-induced obese (DIO) mice.