3,3-dimethyl-1-(3-nitropyridin-2-yl)indoline | 870072-64-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3,3-dimethyl-1-(3-nitropyridin-2-yl)indoline
• 英文别名: 3,3-Dimethyl-1-(3-nitropyridin-2-yl)-2,3-dihydro-1H-indole；3,3-dimethyl-1-(3-nitropyridin-2-yl)-2H-indole
• CAS: 870072-64-3
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: QDYZCIFNKLETHX-UHFFFAOYSA-N

物化性质

• 沸点：
  413.3±40.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  62
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-dimethyl-1-(3-nitropyridin-2-yl)indoline 在 钯 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以to afford 4b (20 mg, 76%) as a yellowish powder的产率得到2-(3,3-dimethylindolin-1-yl)pyridin-3-amine
  参考文献：
  名称：

  N-linked heterocyclic antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions

  摘要：

  本发明提供了一种新型尿素，其中包含式(I)的N-芳基或N-杂环芳基取代的杂环，或其立体异构体、互变异构体、药学上可接受的盐或溶剂形式，其中变量A、B、D和W如本文所定义。这些化合物是选择性抑制人P2Y1受体的药物。

  公开号：

  US08329718B2
• 作为产物：
  描述：

  N-乙酰基-2-羟基吲哚 在 lithium aluminium tetrahydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 3,3-dimethyl-1-(3-nitropyridin-2-yl)indoline
  参考文献：
  名称：

  Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a Potent, Selective, and Bioavailable P2Y₁ Antagonist

  摘要：

  Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y(1) antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y(12) antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y(1) antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 31 will also be presented. Compound 31 was our first P2Y(1) antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.

  DOI：

  10.1021/jm4013906

文献信息

• Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions
  申请人：Tuerdi Huji

  公开号：US20050261244A1

  公开（公告）日：2005-11-24

  The present invention provides novel ureas containing N-aryl or N-heteroaryl substituted heterocycles and analogues thereof, which are selective inhibitors of the human P2Y 1 receptor. The invention also provides for various pharmaceutical compositions of the same and methods for treating diseases responsive to modulation of P2Y 1 receptor activity.

  本发明提供了含有N-芳基或N-杂环芳基取代的杂环化合物及其类似物的新型脲类化合物，这些化合物是人类P2Y1受体的选择性抑制剂。该发明还提供了相应的各种药物组合物以及调节P2Y1受体活性治疗对其敏感的疾病的方法。
• N-LINKED HETEROCYCLIC ANTAGONISTS OF P2Y1 RECEPTOR USEFUL IN THE TREATMENT OF THROMBOTIC CONDITIONS
  申请人：Qiao Jennifer

  公开号：US20100197716A1

  公开（公告）日：2010-08-05

  The present invention provides novel ureas containing N-aryl or N-heteroaryl substituted heterocycles of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, B, D and W are as defined herein. These compounds are selective inhibitors of the human P2Y 1 receptor which can be used as medicaments.

  本发明提供了一种新型尿素，包含式（I）中的N-芳基或N-杂环芳基取代的杂环，或其立体异构体、互变异构体、药学上可接受的盐或溶剂形式，其中变量A、B、D和W如本文所定义。这些化合物是人类P2Y1受体的选择性抑制剂，可用作药物。
• UREA ANTAGONISTS OF P2Y1 RECEPTOR USEFUL IN THE TREATMENT OF THROMBOTIC CONDITIONS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1750704B1

  公开（公告）日：2009-07-22
• US7550499B2
  申请人：——

  公开号：US7550499B2

  公开（公告）日：2009-06-23
• US7728008B2
  申请人：——

  公开号：US7728008B2

  公开（公告）日：2010-06-01