tert-butyl 4-((5-bromopyrazin-2-yl)oxy)piperidine-1-carboxylate | 832735-47-4

• 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: tert-butyl 4-((5-bromopyrazin-2-yl)oxy)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(5-bromopyrazin-2-yloxy)piperidine-1-carboxylate；tert-butyl 4-(5-bromopyrazin-2-yl)oxypiperidine-1-carboxylate
• CAS: 832735-47-4
• 化学式: C₁₄H₂₀BrN₃O₃
• 分子量: 358.235
• InChiKey: CTGDSCTYXKZUOI-UHFFFAOYSA-N

物化性质

• 沸点：
  417.5±45.0 °C(Predicted)
• 密度：
  1.394±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((5-bromopyrazin-2-yl)oxy)piperidine-1-carboxylate 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二甲基亚砜 、 甲苯 为溶剂， 反应 30.0h， 生成 N-(diphenylmethylidene)-5-[4-({5-[(diphenylmethylidene)amino]pyrazin-2-yl}oxy)piperidin-1-yl]pyrazin-2-amine
  参考文献：
  名称：

  Design and evaluation of novel glutaminase inhibitors

  摘要：

  A novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved ClogPs, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.009
• 作为产物：
  描述：

  2,5-二溴吡嗪 、 N-Boc-4-羟基哌啶 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以74%的产率得到tert-butyl 4-((5-bromopyrazin-2-yl)oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Design and evaluation of novel glutaminase inhibitors

  摘要：

  A novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved ClogPs, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.009

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY<br/>[FR] COMPOSES ET COMPOSITIONS COMME MODULATEURS DE L'ACTIVITE DE GPR119
  申请人：IRM LLC

  公开号：WO2011044001A1

  公开（公告）日：2011-04-14

  The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.

  这项发明提供了化合物，包括这些化合物的药物组合物，以及使用这些化合物治疗或预防与GPR119活性相关的疾病或紊乱的方法。
• Discovery and biological evaluation of novel G protein‐coupled receptor 119 agonists for type 2 diabetes
  作者：Ying Zhou、Youzhi Wang、Leilei Zhang、Chunlei Tang、Bainian Feng

  DOI：10.1002/ardp.201800267

  日期：2019.4

  protein‐coupled receptor 119 (GPR119) is a member of the GPCR family promising to be the target for type 2 diabetes mellitus (T2DM) treatment. In this work, 30 novel compounds were designed, synthesized, and evaluated by in vitro cAMP activation assay, where compounds II–14 and II–18 showed the best potency with EC50 values of 69 and 99 nM, respectively. In the oral glucose tolerance test, compound II–18 showed

  G 蛋白偶联受体 119 (GPR119) 是 GPCR 家族的成员，有望成为 2 型糖尿病 (T2DM) 治疗的靶点。在这项工作中，设计、合成了 30 种新型化合物，并通过体外 cAMP 激活试验进行了评估，其中化合物 II-14 和 II-18 显示出最佳效力，EC50 值分别为 69 和 99 nM。在口服葡萄糖耐量试验中，在 30 mg/kg 的固定剂量下，化合物 II-18 在降低血液漂移方面比 MBX-2982 更有效。在这里，我们报告化合物 II-18 具有优异的激动活性和降低血糖偏差的口服有效活性，可作为治疗 T2DM 的有效 GPR119 激动剂。
• Heteroaryloxy nitrogenous saturated heterocyclic derivative
  申请人：Ohtake Norikazu

  公开号：US20060178375A1

  公开（公告）日：2006-08-10

  Compound of the formula: (I) [wherein each of X 1 , X 2 , and X 3 independently represents N or CH, W represents the formula (II):(II) or the formula (III):(III) and Y represents a group of the formula (IV):(IV)], or a pharmacologically acceptable salt thereof. This compound exhibits histamine receptor H3 antagonist or inverse agonist activity and is useful of the treatment and/or prevention of obesity, diabetes, hormonal secretion abnormality, sleep, disorder, etc.

  该化合物的化学式为（I），其中X1、X2和X3分别独立地代表N或CH，W代表式（II）：（II）或式（III）：（III），Y代表式（IV）的基团：（IV），或其药学上可接受的盐。该化合物表现出组胺H3受体拮抗剂或倒向激动剂活性，可用于治疗和/或预防肥胖症、糖尿病、激素分泌异常、睡眠障碍等疾病。
• COMPOUNDS AND COMPOSITIONS AS MODULATORS OF GPR119 ACTIVITY
  申请人：Azimioara Mihai

  公开号：US20110245220A1

  公开（公告）日：2011-10-06

  The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.

  该发明提供了化合物，包括这些化合物的制药组合物和使用这些化合物治疗或预防与GPR119活性相关的疾病或障碍的方法。
• Compounds and compositions as modulators of GPR119 activity
  申请人：Azimioara Mihai

  公开号：US08575168B2

  公开（公告）日：2013-11-05

  The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of GPR119.

  该发明提供了化合物，包括这些化合物的药物组合物和使用这些化合物治疗或预防与GPR119活性相关的疾病或疾病的方法。