9-(2-甲氧基-2-氧代乙基)-3-氮杂螺[5.5]十一烷-3-羧酸叔丁酯 | 1346229-41-1

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 中文名称: 9-(2-甲氧基-2-氧代乙基)-3-氮杂螺[5.5]十一烷-3-羧酸叔丁酯
• 英文名称: tert-butyl 9-(2-methoxy-2-oxoethyl)-3-azaspiro[5.5]undecane-3-carboxylate
• 英文别名: tert-Butyl 9-(2-methoxy-2-oxoethyl)-3-azaspiro[5.5]undecane-3-carboxylate
• CAS: 1346229-41-1
• 化学式: C₁₈H₃₁NO₄
• 分子量: 325.448
• InChiKey: VEYMCZKGXQGOPU-UHFFFAOYSA-N

物化性质

• 沸点：
  409.1±18.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933790090

反应信息

• 作为反应物：
  描述：

  9-(2-甲氧基-2-氧代乙基)-3-氮杂螺[5.5]十一烷-3-羧酸叔丁酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以91%的产率得到2-(3-氮杂螺[5.5]十一烷-9-基)乙酸盐酸盐甲酯
  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：

  4-甲酰基-N-CBZ 哌啶 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 甲基叔丁基醚 、 异丙醇 为溶剂， 50.0 ℃ 、344.75 kPa 条件下， 反应 27.5h， 生成 9-(2-甲氧基-2-氧代乙基)-3-氮杂螺[5.5]十一烷-3-羧酸叔丁酯
  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

• SPIROCYCLIC COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
  申请人：ADVINUS THERAPEUTICS LIMITED

  公开号：US20150218187A1

  公开（公告）日：2015-08-06

  The present disclosure relates to a series of spirocyclic compounds of formula (I), their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates, hydrates, N-Oxides, Co crystals and formulations thereof. The disclosure also relates to process of preparation of these spirocyclic compounds. These compounds are useful in the treatment, prevention, prophylaxis, management, or adjunct treatment of all medical conditions related to inhibition of acyl CoA diacyl glycerol acyltransferase 1 (DGAT1).

  本公开涉及一系列公式（I）的螺环化合物及其立体异构体、互变异构体、前药、药学上可接受的盐、多晶形、溶剂化物、水合物、N-氧化物、共晶体和制剂。本公开还涉及制备这些螺环化合物的过程。这些化合物在治疗、预防、预防、管理或辅助治疗与抑制酰基辅酶A二酰甘油酰转移酶1（DGAT1）有关的所有医疗条件方面是有用的。
• 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。
• [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：WO2014059232A3

  公开（公告）日：2015-07-16
• US9550793B2
  申请人：——

  公开号：US9550793B2

  公开（公告）日：2017-01-24
• US9708270B2
  申请人：——

  公开号：US9708270B2

  公开（公告）日：2017-07-18