ethyl 2-(8-methyl-3-azaspiro[5.5]undecan-9-yl)acetate | 1599479-12-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-(8-methyl-3-azaspiro[5.5]undecan-9-yl)acetate
• 英文别名: Ethyl 2-(10-methyl-3-azaspiro[5.5]undecan-9-yl)acetate
• CAS: 1599479-12-5
• 化学式: C₁₅H₂₇NO₂
• 分子量: 253.385
• InChiKey: SKYFHMKFYLRABU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-(8-methyl-3-azaspiro[5.5]undecan-9-yl)acetate 在 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 2-(3-(2-chloro-5-(trifluoromethoxy)phenyl)-8-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
• 作为产物：
  描述：

  N-Cbz-9-氧代-3-氮杂螺[5.5]十一烷 在 20% palladium hydroxide-activated charcoal 、 氢气 、 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成 ethyl 2-(8-methyl-3-azaspiro[5.5]undecan-9-yl)acetate
  参考文献：
  名称：

  [EN] SUBSTITUTED SPIROPIPERIDINYL COMPOUNDS USEFUL AS GPR120 AGONISTS
  [FR] COMPOSÉS SPIROPIPÉRIDINYLIQUES SUBSTITUÉS UTILES COMME AGONISTES DE GPR120

  摘要：

  公开号：

  WO2014059232A3

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