1-(2H-pyrido-[3,2-b][1,4]oxazin-4(3H)-yl)ethanone | 89970-14-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2H-pyrido-[3,2-b][1,4]oxazin-4(3H)-yl)ethanone
• 英文别名: 1-(2H-pyrido[3,2-b][1,4]oxazin-4(3H)-yl)ethyl ketone；3,4-Dihydro-4-acetyl-2H-pyrido(3,2-b)-1,4-oxazine；1-(2,3-dihydropyrido[3,2-b][1,4]oxazin-4-yl)ethanone
• CAS: 89970-14-9
• 化学式: C₉H₁₀N₂O₂
• 分子量: 178.191
• InChiKey: WFIMERAIUXNFGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2H-pyrido-[3,2-b][1,4]oxazin-4(3H)-yl)ethanone 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) N-溴代丁二酰亚胺(NBS) 、 锌 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 3,4-dihydro-2H-pyrido-[3,2-b][1,4]oxazine-7-carbonitrile
  参考文献：
  名称：

  Acridone-Based Inhibitors of Inosine 5‘-Monophosphate Dehydrogenase:  Discovery and SAR Leading to the Identification of N-(2-(6-(4-Ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)

  摘要：

  Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.

  DOI：

  10.1021/jm070299x
• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 在 吡啶 、 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 0.08h， 生成 1-(2H-pyrido-[3,2-b][1,4]oxazin-4(3H)-yl)ethanone
  参考文献：
  名称：

  Acridone-Based Inhibitors of Inosine 5‘-Monophosphate Dehydrogenase:  Discovery and SAR Leading to the Identification of N-(2-(6-(4-Ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)

  摘要：

  Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.

  DOI：

  10.1021/jm070299x

文献信息

• HETEROCYCLIC PYRIDONE COMPOUND, AND INTERMEDIATE, PREPARATION METHOD AND USE THEREOF
  申请人：Cheng Jianjun

  公开号：US20140206679A1

  公开（公告）日：2014-07-24

  The present invention relates to a heterocyclic pyridone compound represented by General Formula (I), where the heterocyclic pyridone compound is used as a tyrosine kinase inhibitor, and particularly a c-Met inhibitor. The present invention also relates to intermediates for preparing heterocyclic pyridone compound and a preparation method. The present invention further relates to a pharmaceutical composition containing the heterocyclic pyridone compound as an active ingredient, and a use of the pharmaceutical composition in treatment of diseases associated with tyrosine kinase c-Met, especially cancer associated with c-Met, as a medicament.

  本发明涉及一种由通式(I)表示的杂环吡啶酮化合物，其中该杂环吡啶酮化合物用作酪氨酸激酶抑制剂，特别是c-Met抑制剂。本发明还涉及用于制备杂环吡啶酮化合物的中间体和制备方法。本发明还涉及一种包含杂环吡啶酮化合物作为活性成分的药物组合物，以及药物组合物在治疗与酪氨酸激酶c-Met相关的疾病，特别是与c-Met相关的癌症作为药物的用途。
• US7312209B2
  申请人：——

  公开号：US7312209B2

  公开（公告）日：2007-12-25
• US9562060B2
  申请人：——

  公开号：US9562060B2

  公开（公告）日：2017-02-07
• Acridone-Based Inhibitors of Inosine 5‘-Monophosphate Dehydrogenase:  Discovery and SAR Leading to the Identification of <i>N</i>-(2-(6-(4-Ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
  作者：Scott H. Watterson、Ping Chen、Yufen Zhao、Henry H. Gu、T. G. Murali Dhar、Zili Xiao、Shelley K. Ballentine、Zhongqi Shen、Catherine A. Fleener、Katherine A. Rouleau、Mary Obermeier、Zheng Yang、Kim W. McIntyre、David J. Shuster、Mark Witmer、Donna Dambach、Sam Chao、Arvind Mathur、Bang-Chi Chen、Joel C. Barrish、Jeffrey A. Robl、Robert Townsend、Edwin J. Iwanowicz

  DOI：10.1021/jm070299x

  日期：2007.7.1

  Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.