tert-butyl 9-(methoxymethylene)-3-azaspiro[5.5]undecane-3-carboxylate | 1416176-13-0

• 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
• 英文名称: tert-butyl 9-(methoxymethylene)-3-azaspiro[5.5]undecane-3-carboxylate
• 英文别名: tert-butyl 9-(methoxymethylidene)-3-azaspiro[5.5]undecane-3-carboxylate
• CAS: 1416176-13-0
• 化学式: C₁₇H₂₉NO₃
• 分子量: 295.422
• InChiKey: PHGNMZYFCWWFPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 9-(methoxymethylene)-3-azaspiro[5.5]undecane-3-carboxylate 在 盐酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 3-azaspiro[5.5]undecane-9-carbaldehyde
  参考文献：
  名称：

  WEE1 DEGRADING COMPOUNDS

  摘要：

  Provided herein are compounds which target WEE1 kinase proteins for ubiquitination and proteasomal degradation. Also provided herein are methods for using said compounds for the treatment of diseases.

  公开号：

  WO2024146502A1
• 作为产物：
  描述：

  3-BOC-9-氧代-3-氮杂螺[5.5]十一烷 、 甲氧基甲基三苯基氯化膦 在 potassium tert-butylate 作用下， 以 甲苯 为溶剂， 反应 0.33h， 以44%的产率得到tert-butyl 9-(methoxymethylene)-3-azaspiro[5.5]undecane-3-carboxylate
  参考文献：
  名称：

  新型7-氮杂螺[3.5]壬烷衍生物作为GPR119激动剂的设计，合成及生物学评价

  摘要：

  描述了新型7-氮杂螺[3.5]壬烷GPR119激动剂的设计和合成。在该系列中，右哌啶N封端基团（R 2）和左芳基基团（R 3）的优化导致将化合物54g鉴定为有效的GPR119激动剂。化合物54g在Sprague-Dawley（SD）大鼠中显示出理想的PK分布，在糖尿病大鼠中表现出良好的降糖效果。

  DOI：

  10.1016/j.bmc.2018.02.032

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。
• 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.
• [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
• US9708270B2
  申请人：——

  公开号：US9708270B2

  公开（公告）日：2017-07-18