N-(6-(5-benzyl-4-hydroxy-6-methylpyrimidin-2-yl)pyridin-3-yl)-2-chloroacetamide | 1116016-62-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(6-(5-benzyl-4-hydroxy-6-methylpyrimidin-2-yl)pyridin-3-yl)-2-chloroacetamide
• 英文别名: n-(6-(5-Benzyl-4-hydroxy-6-methylpyrimidin-2-yl)pyridin-3-yl)-2-chloroacetamide；N-[6-(5-benzyl-4-methyl-6-oxo-1H-pyrimidin-2-yl)pyridin-3-yl]-2-chloroacetamide
• CAS: 1116016-62-6
• 化学式: C₁₉H₁₇ClN₄O₂
• 分子量: 368.823
• InChiKey: IDOAXXIIOYRVNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  83.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(5-aminopyridin-2-yl)-5-benzyl-6-methylpyrimidin-4-ol 、 氯乙酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以63%的产率得到N-(6-(5-benzyl-4-hydroxy-6-methylpyrimidin-2-yl)pyridin-3-yl)-2-chloroacetamide
  参考文献：
  名称：

  [EN] PYRIDYL DERIVATIVES, THEIR PREPARATION AND USE
  [FR] DÉRIVÉS DE PYRIDYLE, LEUR PRÉPARATION ET UTILISATION.

  摘要：

  本发明涉及能够抑制磷脂酰肌醇-3-激酶（PI3k）、哺乳动物雷帕霉素靶蛋白（mTOR）和/或缺氧诱导因子1α（HIF-1α）介导信号的吡啶基衍生物。还公开了制备吡啶基衍生物的方法，以及它们在制造用于治疗由PI3K、mTOR和HIF-1α途径中的一个或多个信号通路失调引起的临床病症的药物组合物中的用途。吡啶基衍生物还可用于治疗由TNF-α介导的疾病或紊乱。

  公开号：

  WO2009019656A1

文献信息

• [EN] PYRIDYL DERIVATIVES, THEIR PREPARATION AND USE<br/>[FR] DÉRIVÉS DE PYRIDYLE, LEUR PRÉPARATION ET UTILISATION.
  申请人：PIRAMAL LIFE SCIENCES LTD

  公开号：WO2009019656A1

  公开（公告）日：2009-02-12

  The present invention relates to pyridyl derivatives capable of inhibiting phosphatidylinositol-3-kinase (PI3k), mammalian target of rapamycin (mTOR) and/or hypoxia inducible factor 1α (HIF-1α) mediated signaling. Also disclosed are processes for preparation of the pyridyl derivatives, and their use in the manufacture of pharmaceutical compositions for the treatment of clinical conditions caused by deregulation of signaling pathways selected from one or more of PI3K, mTOR and HIF-1α pathways. The pyridyl derivatives are also useful for the treatment of conditions or disorders mediated by TNF-α.

  本发明涉及能够抑制磷脂酰肌醇-3-激酶（PI3k）、哺乳动物雷帕霉素靶蛋白（mTOR）和/或缺氧诱导因子1α（HIF-1α）介导信号的吡啶基衍生物。还公开了制备吡啶基衍生物的方法，以及它们在制造用于治疗由PI3K、mTOR和HIF-1α途径中的一个或多个信号通路失调引起的临床病症的药物组合物中的用途。吡啶基衍生物还可用于治疗由TNF-α介导的疾病或紊乱。
• PYRIDYL DERIVATIVES, THEIR PREPARATION AND USE
  申请人：Kumar Sanjay

  公开号：US20110077252A1

  公开（公告）日：2011-03-31

  The present invention relates to pyridyl derivatives capable of inhibiting phosphatidylinositol-3-kinase (PI3k), mammalian target of rapamycin (mTOR) and/or hypoxia inducible factor 1α (HIF-1α) mediated signaling. Also disclosed are processes for preparation of the pyridyl derivatives, and their use in the manufacture of pharmaceutical compositions for the treatment of clinical conditions caused by deregulation of signaling pathways selected from one or more of PI3K, mTOR and HIF-1α pathways. The pyridyl derivatives are also useful for the treatment of conditions or disorders mediated by TNF-α.

  本发明涉及能够抑制磷脂酰肌醇-3-激酶（PI3k）、哺乳动物雷帕霉素靶蛋白（mTOR）和/或缺氧诱导因子1α（HIF-1α）介导信号的吡啶衍生物。还披露了制备吡啶衍生物的过程，并将其用于制造用于治疗由PI3K、mTOR和HIF-1α途径中一个或多个信号通路失调引起的临床情况的制药组合物。吡啶衍生物还可用于治疗由TNF-α介导的疾病或紊乱。
• Pyridyl derivatives, their preparation and use
  申请人：Piramal Enterprises Limited

  公开号：US08314103B2

  公开（公告）日：2012-11-20

  The present invention relates to pyridyl derivatives capable of inhibiting phosphatidylinositol-3-kinase (PI3k), mammalian target of rapamycin (mTOR) and/or hypoxia inducible factor 1α (HIF-1α) mediated signaling. Also disclosed are processes for preparation of the pyridyl derivatives, and their use in the manufacture of pharmaceutical compositions for the treatment of clinical conditions caused by deregulation of signaling pathways selected from one or more of PI3K, mTOR and HIF-1α pathways. The pyridyl derivatives are also useful for the treatment of conditions or disorders mediated by TNF-α.

  本发明涉及一种能够抑制磷脂酰肌醇-3-激酶（PI3K）、哺乳动物雷帕霉素靶蛋白（mTOR）和/或缺氧诱导因子1α（HIF-1α）介导信号的吡啶基衍生物。还公开了制备吡啶基衍生物的过程，以及它们在制造用于治疗由PI3K、mTOR和HIF-1α途径中一个或多个信号通路失调引起的临床病症的药物组合物方面的用途。吡啶基衍生物还可用于治疗由TNF-α介导的病症或紊乱。
• US8314103B2
  申请人：——

  公开号：US8314103B2

  公开（公告）日：2012-11-20
• Development of novel inhibitors targeting HIF-1α towards anticancer drug discovery
  作者：Nilambari Yewalkar、Vijaykumar Deore、Amol Padgaonkar、Sonal Manohar、Bichismita Sahu、Pramod Kumar、Archana Jalota-Badhwar、Kalpana S. Joshi、Somesh Sharma、Sanjay Kumar

  DOI：10.1016/j.bmcl.2010.09.083

  日期：2010.11

  Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a critical regulatory protein of cellular response to hypoxia, and regulates the transcription of many genes involved in key aspects of cancer biology, including immortalization, maintenance of stem cell pools, cellular dedifferentiation, vascularization, and invasion/metastasis. HIF-1 alpha has been implicated in the regulation of genes involved in angiogenesis, for example, VEGF and is associated with tumor progression. In the last decade, over expression of HIF-1 alpha has been demonstrated in many common human cancers and emerging as a validated target for anticancer drug discovery. Here we report the discovery of newly designed and synthesized pyridylpyrimidine based potent and selective inhibitors of HIF-1 alpha. P2630 has been found as potent antiproliferative, antiangiogenic and orally efficacious compound in PC-3 xenograft mice model. (C) 2010 Elsevier Ltd. All rights reserved.