5-nitro-2-pyrrolidin-1-yl-3H-pyrimidin-4-one | 1562399-11-4

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 5-nitro-2-pyrrolidin-1-yl-3H-pyrimidin-4-one
• 英文别名: 5-nitro-2-(pyrrolidin-1-yl)-4(3H)-pyrimidinone；5-nitro-2-pyrrolidin-1-yl-1H-pyrimidin-6-one
• CAS: 1562399-11-4
• 化学式: C₈H₁₀N₄O₃
• 分子量: 210.192
• InChiKey: UPERKEYJSOMYSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-nitro-2-pyrrolidin-1-yl-3H-pyrimidin-4-one 在 盐酸 、 copper(l) iodide 、 三乙胺 、 对甲苯磺酰氯 、 tin(ll) chloride 、 N,N'-二甲基乙二胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 1-(2-Pyrrolidin-1-ylpyrimido[4,5-b][1,4]benzothiazin-5-yl)ethanone
  参考文献：
  名称：

  Diazaphenoxazines and Diazaphenothiazines: Synthesis of the “Correct” Isomers Reveals They Are Highly Reactive Radical-Trapping Antioxidants

  摘要：

  The preparation of 2,4-diazaphenothiazines and 2,4-diazaphenoxazines via a copper-catalyzed intramolecular amination is described. Literature approaches-mhich utilize easily accessed (2'-aminophenyl) 4-pyri(mi)dyl sulfides undergo a Smiles rearrangement that gives rise to the 1,3-dinza derivatives instead, confirmed by X-ray crystallography. Inversion of the polarity of the cyclization avoids the rearrangement and affords the desired,products. Preliminary kinetic studies suggest :that 2,4-diazaphenothiazines and diazaphenoxazines, but not the 1,3-diaza isomers, are remarkably potent radical-trapping antioxidants.

  DOI：

  10.1021/acs.orglett.7b00615
• 作为产物：
  描述：

  2-(pyrrolidin-1-yl)-4(3H)-pyrimidinone 在 硫酸 、 硝酸 作用下， 以72%的产率得到5-nitro-2-pyrrolidin-1-yl-3H-pyrimidin-4-one
  参考文献：
  名称：

  Diazaphenoxazines and Diazaphenothiazines: Synthesis of the “Correct” Isomers Reveals They Are Highly Reactive Radical-Trapping Antioxidants

  摘要：

  The preparation of 2,4-diazaphenothiazines and 2,4-diazaphenoxazines via a copper-catalyzed intramolecular amination is described. Literature approaches-mhich utilize easily accessed (2'-aminophenyl) 4-pyri(mi)dyl sulfides undergo a Smiles rearrangement that gives rise to the 1,3-dinza derivatives instead, confirmed by X-ray crystallography. Inversion of the polarity of the cyclization avoids the rearrangement and affords the desired,products. Preliminary kinetic studies suggest :that 2,4-diazaphenothiazines and diazaphenoxazines, but not the 1,3-diaza isomers, are remarkably potent radical-trapping antioxidants.

  DOI：

  10.1021/acs.orglett.7b00615

文献信息

• Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects
  作者：Christian Harcken、Doris Riether、Daniel Kuzmich、Pingrong Liu、Raj Betageri、Mark Ralph、Michel Emmanuel、Jonathan T. Reeves、Angela Berry、Donald Souza、Richard M. Nelson、Alison Kukulka、Tazmeen N. Fadra、Ljiljana Zuvela-Jelaska、Roger Dinallo、Jörg Bentzien、Gerald H. Nabozny、David S. Thomson

  DOI：10.1021/jm4019178

  日期：2014.2.27

  Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain "diazaindole" moieties and display different transcriptional regulatory profiles in vitro and are considered "dissociated" between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of (R)-18 and (R)-21. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone 2 in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclinical in vivo model.