ethyl 4-(piperidin-4-yl)benzoate | 741729-98-6

• 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: ethyl 4-(piperidin-4-yl)benzoate
• 英文别名: 4-piperidin-4-yl-ethyl benzoate；ethyl 4-piperidin-4-ylbenzoate
• CAS: 741729-98-6
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: IMMSREKEHZYMFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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 4-(piperidin-4-yl)benzoate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium hydroxide monohydrate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 40.0h， 生成 4-[1-[2-Fluoro-5-(trifluoromethoxy)phenyl]piperidin-4-yl]benzoic 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：

  ethyl 4-(1-benzyl-1,2,5,6-tetrahydropyridin-4-yl)benzoate 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以100%的产率得到ethyl 4-(piperidin-4-yl)benzoate
  参考文献：
  名称：

  10H-吡嗪并[2,3-b] [1,4]苯并噻嗪的哌啶羧酸衍生物作为口服活性黏附分子抑制剂。

  摘要：

  制备了10H-吡嗪并[2,3-b] [1,4]苯并噻嗪的新型哌啶羧酸衍生物，并评价了其对粘附分子如细胞间粘附分子-1（ICAM-1）上调的抑制活性。用含有羧酸的部分取代先前制备的衍生物的哌啶环上的甲磺酰基基团产生了许多有效的粘附分子抑制剂。其中，（反）[3-（10H-吡嗪并[2,3-b] [1,4]苯并噻嗪-8-基）甲基-3-氮杂双环[3.3.1]非-9-基]乙酸2q （ER-49890）在使用小鼠的白介素1（IL-1）诱导的爪炎症模型中显示出对中性粒细胞迁移的最强口服抑制活性，在大鼠角叉菜胶胸膜炎模型中显示了白细胞积累以及对胶原蛋白的治疗作用诱发的大鼠关节炎。

  DOI：

  10.1248/cpb.52.675

文献信息

• Npy antagonists, preparation and uses
  申请人：Botez Iuliana

  公开号：US20090233910A1

  公开（公告）日：2009-09-17

  The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.

  本发明涉及新颖化合物，它们的制备和用途，特别是在治疗方面的用途。更具体地说，它涉及至少具有两个芳香环的衍生化合物，它们的制备和用途，特别是在人类或动物健康领域。这些化合物对存在于中枢和外周神经系统中的神经肽Y（NPY）的生物受体具有亲和力。本发明的化合物优选为NPY拮抗剂，更具体地说是NPY Y1亚型的拮抗剂，因此可用于治疗或预防涉及NPY的任何疾病。本发明还涉及含有所述化合物的药物组合物，其制备和用途，以及使用所述化合物的治疗方法。
• [EN] AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS SULFONAMIDES ET AMIDES AMIDO-SPIROCYCLIQUES
  申请人：GENENTECH INC

  公开号：WO2013127269A1

  公开（公告）日：2013-09-06

  Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  提供了螺环氨基和磺胺基化合物，包括这些化合物的药物组合物，以及使用这些化合物进行治疗的方法。
• Going beyond Binary: Rapid Identification of Protein–Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach
  作者：Katya Nacheva、Sameer S. Kulkarni、Mintesinot Kassu、David Flanigan、Andrii Monastyrskyi、Iredia D. Iyamu、Kenichiro Doi、Megan Barber、Niranjan Namelikonda、Jeremiah D. Tipton、Prakash Parvatkar、Hong-Gang Wang、Roman Manetsch

  DOI：10.1021/acs.jmedchem.3c00108

  日期：——

  Kinetic target-guided synthesis (KTGS) is a powerful screening approach that enables identification of small molecule modulators for biomolecules. While many KTGS variants have emerged, a majority of the examples suffer from limited throughput and a poor signal/noise ratio, hampering reliable hit detection. Herein, we present our optimized multifragment KTGS screening strategy that tackles these limitations

  动力学靶标引导合成 (KTGS) 是一种强大的筛选方法，能够识别生物分子的小分子调节剂。虽然已经出现了许多 KTGS 变体，但大多数示例都受到吞吐量有限和信噪比较差的影响，从而妨碍了可靠的命中检测。在此，我们提出了解决这些限制的优化多片段 KTGS 筛选策略。该方法利用选定的反应监测液相色谱串联质谱法进行命中检测，从而能够在每个筛选孔中孵育 190 个片段组合。因此，我们的片段库从 81 个可能的组合扩展到 1710 个，代表迄今为止组装的最大的 KTGS 筛选库。对扩展的文库进行了针对 Mcl-1 的筛选，最终发现了 24 种抑制剂。这项工作揭示了 KTGS 在快速、可靠地鉴定命中物方面的真正潜力，进一步凸显了其作为药物发现中现有筛选方法的补充的实用性。
• AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES
  申请人：Genentech, Inc.

  公开号：EP2820008A1

  公开（公告）日：2015-01-07
• Piperidine Carboxylic Acid Derivatives of 10H-Pyrazino[2,3-b][1,4]benzothiazine as Orally-Active Adhesion Molecule Inhibitors
  作者：Toshihiko Kaneko、Richard S. J. Clark、Norihito Ohi、Fumihiro Ozaki、Tetsuya Kawahara、Atsushi Kamada、Kazuo Okano、Hiromitsu Yokohama、Masayoshi Ohkuro、Kenzo Muramoto、Osamu Takenaka、Seiichi Kobayashi

  DOI：10.1248/cpb.52.675

  日期：——

  of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect

  制备了10H-吡嗪并[2,3-b] [1,4]苯并噻嗪的新型哌啶羧酸衍生物，并评价了其对粘附分子如细胞间粘附分子-1（ICAM-1）上调的抑制活性。用含有羧酸的部分取代先前制备的衍生物的哌啶环上的甲磺酰基基团产生了许多有效的粘附分子抑制剂。其中，（反）[3-（10H-吡嗪并[2,3-b] [1,4]苯并噻嗪-8-基）甲基-3-氮杂双环[3.3.1]非-9-基]乙酸2q （ER-49890）在使用小鼠的白介素1（IL-1）诱导的爪炎症模型中显示出对中性粒细胞迁移的最强口服抑制活性，在大鼠角叉菜胶胸膜炎模型中显示了白细胞积累以及对胶原蛋白的治疗作用诱发的大鼠关节炎。