3-(4-ethoxyphenyl)-2-[(1R)-1-(pyridin-3-ylmethylamino)ethyl]pyrido[2,3-d]pyrimidin-4-one | 473720-92-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 3-(4-ethoxyphenyl)-2-[(1R)-1-(pyridin-3-ylmethylamino)ethyl]pyrido[2,3-d]pyrimidin-4-one
• CAS: 473720-92-2
• 化学式: C₂₃H₂₃N₅O₂
• 分子量: 401.468
• InChiKey: ZODOCNJSPXPNQD-MRXNPFEDSA-N

物化性质

• 沸点：
  613.8±65.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-ethoxyphenyl)-2-[(1R)-1-(pyridin-3-ylmethylamino)ethyl]pyrido[2,3-d]pyrimidin-4-one 、 4-(三氟甲氧基)苯乙酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-trifluoromethoxyphenyl)-acetamide
  参考文献：
  名称：

  Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3

  摘要：

  A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a I-125-IP10 displacement assay and in in vitro cell migration assays to I P 10, ITAC, and MIG using human peripheral blood mononuclear cells. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.106
• 作为产物：
  描述：

  (R)-[1-(4-oxo-4H-pyrido[2,3-d][1,3]oxazin-2-yl)-ethyl]-carbamic acid tert-butyl ester 在 三乙酰氧基硼氢化钠 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 12.0h， 生成 3-(4-ethoxyphenyl)-2-[(1R)-1-(pyridin-3-ylmethylamino)ethyl]pyrido[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3

  摘要：

  A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a I-125-IP10 displacement assay and in in vitro cell migration assays to I P 10, ITAC, and MIG using human peripheral blood mononuclear cells. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.106

文献信息

• Optimization of a series of quinazolinone-derived antagonists of CXCR3
  作者：Jiwen Liu、Zice Fu、An-Rong Li、Michael Johnson、Liusheng Zhu、Andrew Marcus、Jay Danao、Tim Sullivan、George Tonn、Tassie Collins、Julio Medina

  DOI：10.1016/j.bmcl.2009.07.032

  日期：2009.9

  The evaluation of the CXCR3 antagonist AMG 487 in clinic trials was complicated due to the formation of an active metabolite. In this Letter, we will discuss the further optimization of the quinazolinone series that led to the discovery of compounds devoid of the formation of the active metabolite that was seen with AMG 487. In addition, these compounds also feature increased potency and good pharmacokinetic properties. We will also discuss the efficacy of the lead compound 34 in a mouse model of cellular recruitment induced by bleomycin. (C) 2009 Elsevier Ltd. All rights reserved.
• Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3
  作者：Michael Johnson、An-Rong Li、Jiwen Liu、Zice Fu、Liusheng Zhu、Shichang Miao、Xuemei Wang、Qingge Xu、Alan Huang、Andrew Marcus、Feng Xu、Karen Ebsworth、Emmanuel Sablan、Jay Danao、Jeff Kumer、Dan Dairaghi、Chris Lawrence、Tim Sullivan、George Tonn、Thomas Schall、Tassie Collins、Julio Medina

  DOI：10.1016/j.bmcl.2007.03.106

  日期：2007.6

  A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been synthesized and their affinity for the receptor evaluated. Compounds were evaluated in a I-125-IP10 displacement assay and in in vitro cell migration assays to I P 10, ITAC, and MIG using human peripheral blood mononuclear cells. (c) 2007 Elsevier Ltd. All rights reserved.