3,4-dihydro-2H-pyrido-[3,2-b][1,4]oxazine-7-carbonitrile | 34945-66-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3,4-dihydro-2H-pyrido-[3,2-b][1,4]oxazine-7-carbonitrile
• 英文别名: 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonitrile；3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonitrile；3,4-Dihydro-2H-pyrido<3,2-b>-1,4-oxazin-7-carbonitril
• CAS: 34945-66-9
• 化学式: C₈H₇N₃O
• 分子量: 161.163
• InChiKey: YURHKHQTVHXOKY-UHFFFAOYSA-N

物化性质

• 沸点：
  345.2±42.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-2H-pyrido-[3,2-b][1,4]oxazine-7-carbonitrile 在 镍 氨 、 氢气 作用下， 以 乙醇 为溶剂， 生成 C-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-methylamine
  参考文献：
  名称：

  Clauson-Kaas,N. et al., Acta Chemica Scandinavica (1947), 1971, vol. 25, p. 3135 - 3143

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 锌 作用下， 以 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 1.08h， 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

文献信息

• An expedient Pd/DBU mediated cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6]
  作者：Dengyou Zhang、Haifeng Sun、Lei Zhang、Yu Zhou、Chunpu Li、Hualiang Jiang、Kaixian Chen、Hong Liu

  DOI：10.1039/c2cc17468e

  日期：——

  A practical Pd(PPh3)4/DBU catalytic system for the synthesis of pharmaceutically relevant aminopyridine nitrile intermediates, as well as a variety of other aryl nitriles using non-toxic K4[Fe(CN)6] has been developed. The key features of our new protocol for cyanation lie in that the reaction can be carried out with readily available Pd(PPh3)4 under mild and green conditions, even without the assistance of other ligands.

  一种用于合成具有药物相关性的氨基吡啶腈中间体的实用Pd(PPh3)4/DBU催化体系，以及其他多种使用无毒K4[Fe(CN)6]的芳基腈，已经开发出来。我们新方案中氰化的关键特点在于，反应可以在温和且环保的条件下，使用易于获得的Pd(PPh3)4进行，甚至无需其他配体的辅助。
• US7312209B2
  申请人：——

  公开号：US7312209B2

  公开（公告）日：2007-12-25
• 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.
• Clauson-Kaas,N. et al., Acta Chemica Scandinavica (1947), 1971, vol. 25, p. 3135 - 3143
  作者：Clauson-Kaas,N. et al.

  DOI：——

  日期：——