tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate | 1104444-17-8

• 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-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate
• 英文别名: tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate；tert-butyl 4-(2-chloropyrimidin-4-yl)oxypiperidine-1-carboxylate
• CAS: 1104444-17-8
• 化学式: C₁₄H₂₀ClN₃O₃
• 分子量: 313.784
• InChiKey: UVCZXZCHBRVVNA-UHFFFAOYSA-N

物化性质

• 沸点：
  450.5±35.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 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-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate 在 caesium carbonate 、 三氟乙酸 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 18.5h， 生成 propan-2-yl 4-({2-[5-(methylsulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists

  摘要：

  GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl) indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl] propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-({1-[3-(propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2,3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.028
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 N-Boc-4-羟基哌啶 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.34h， 以26%的产率得到tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate
  参考文献：
  名称：

  PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS

  摘要：

  提供了一些新的化合物，它们是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR 119 G蛋白偶联受体调节剂疗法的疾病方面非常有用。这些新的化合物具有结构式I或结构式IA。

  公开号：

  US20090023702A1

文献信息

• [EN] SUBSTITUTED PYRIDINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS<br/>[FR] INHIBITEURS À PYRIDINE SUBSTITUÉE DE LA TYROSINE KINASE DE LA RATE (SYK)
  申请人：MERCK SHARP & DOHME

  公开号：WO2013192098A1

  公开（公告）日：2013-12-27

  The invention provides certain substituted pyridines of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, Rcy,Cy, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.

  该发明提供了Formula (I)中的某些取代吡啶化合物或其药用可接受的盐，其中R1、R2、R3、R4、Rcy、Cy和t如本文所定义。该发明还提供了包括这些化合物的药物组合物，以及利用这些化合物治疗由脾酪氨酸激酶（Syk）介导的疾病或症状的方法。
• 2,3,4,6-TETRA-SUBSTITUTED BENZENE-1,5-DIAMINE DERIVATIVES, PREPARATION METHOD THEREFOR AND MEDICINAL USE THEREOF
  申请人：SHANGHAI HAIYAN PHARMACEUTICAL TECHNOLOGY CO., LTD.

  公开号：US20170057957A1

  公开（公告）日：2017-03-02

  The present invention relates to 2,3,4,6-tetra-substituted benzene-1,5-diamine derivatives, a preparation method therefor and a medicinal use thereof. Specifically, disclosed are compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method therefor and application thereof. Definition of each group in the formula can be found in the specification for details.

  本发明涉及2,3,4,6-四取代苯-1,5-二胺衍生物，其制备方法及药用。具体公开了式(I)化合物或药用可接受的盐、立体异构体、溶剂合物或前药，其制备方法和应用。公式中每个基团的定义详见说明书。
• PYRIDONE GPR119 G PROTEIN-COUPLED RECEPTOR AGONISTS
  申请人：Wacker Dean A.

  公开号：US20090023702A1

  公开（公告）日：2009-01-22

  Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR 119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.

  提供了一些新的化合物，它们是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR 119 G蛋白偶联受体调节剂疗法的疾病方面非常有用。这些新的化合物具有结构式I或结构式IA。
• [EN] AMINOPYRIMIDINES AS SYK INHIBITORS<br/>[FR] AMINOPYRIMIDINES EN TANT QU'INHIBITEURS DE LA SYK
  申请人：MERCK SHARP & DOHME

  公开号：WO2011075560A1

  公开（公告）日：2011-06-23

  The present invention provides novel pyrimidine amines of formula (I) which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis.

  本发明提供了式（I）的新型嘧啶胺化合物，它们是脾酪氨酸激酶的有效抑制剂，并可用于治疗和预防由该酶介导的疾病，如哮喘、慢性阻塞性肺病（COPD）和类风湿性关节炎。
• [EN] PHARMACEUTICAL COMPOUNDS AS INHIBITORS OF SPHINGOSINE KINASE<br/>[FR] COMPOSÉS PHARMACEUTIQUES EN TANT QU'INHIBITEURS DE LA SPHINGOSINE KINASE
  申请人：ALMAC DISCOVERY LTD

  公开号：WO2012069852A1

  公开（公告）日：2012-05-31

  The present invention relates to compounds that are useful as inhibitors of the activity of one or more isoforms of sphingosine kinase. Particularly, although not exclusively, the present invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment and/or prevention of cancers, hyperproliferative, inflammatory, angiogenic, immune and viral infectious diseases.

  本发明涉及一种可用作抑制一种或多种鞘氨醇激酶同工酶活性的化合物。特别是，尽管不仅限于此，本发明还涉及包含这些化合物的药物组合物，以及将这些化合物用于治疗和/或预防癌症、高增殖、炎症、血管生成、免疫和病毒感染性疾病的用途。