N-(5-(1-(4-nitrobenzyl)piperidin-4-yl)-2-isopropoxyphenyl)pyrazine-2-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(5-(1-(4-nitrobenzyl)piperidin-4-yl)-2-isopropoxyphenyl)pyrazine-2-carboxamide
• 英文别名: N-[5-[1-[(4-nitrophenyl)methyl]piperidin-4-yl]-2-propan-2-yloxyphenyl]pyrazine-2-carboxamide
• 化学式: C₂₆H₂₉N₅O₄
• 分子量: 475.547
• InChiKey: GGADRAUNTVDAND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(5-(1-(4-nitrobenzyl)piperidin-4-yl)-2-isopropoxyphenyl)pyrazine-2-carboxamide 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、393.01 kPa 条件下， 反应 24.0h， 生成 N-(5-(1-(4-aminobenzyl)piperidin-4-yl)-2-isopropoxyphenyl)pyrazine-2-carboxamide
  参考文献：
  名称：

  Design, syntheses, and characterization of pharmacophore based chemokine receptor CCR5 antagonists as anti prostate cancer agents

  摘要：

  Accumulating evidence has shown multiple roles that chemokine receptor CCR5 may play to promote the progression of several types of cancer. The mechanism of such promotion is believed to involve chronic inflammation that creates a microenvironment which enhances tumor survival. Therefore, blocking CCR5 function with an antagonist may provide a novel treatment of cancers such as prostate cancer. Currently, several CCR5 antagonists are available, but all have been optimized for their inhibitory activity on HIV-1 cellular membrane invasion process rather than inhibition on cytoplasmic signaling pathways. Thus, there is need to develop CCR5 antagonists focusing on blockage of CCR5 downstream signaling and inhibition of CCR5 related prostate cancer proliferation and progression. In this report, a pharmacophore analysis was conducted based on docking studies of several known CCR5 antagonists in a CCR5 homology model. A unique structural skeleton for CCR5 antagonist was constructed and functionalized, resulting in a new series of small molecules to be synthesized and characterized. A combination of CCR5 calcium flux inhibition, anti prostate cancer cell proliferation, basal cytotoxicity, and in vivo animal model studies were applied to screen the newly synthesized compounds. Results from this study provided a potential lead compound for future CCR5 antagonist development focusing on prostate cancer therapy. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2013.09.004
• 作为产物：
  描述：

  1-溴-4-异丙氧基苯 在 吡啶 、 5%-palladium/activated carbon 、 氢气 、 碘 、 硝酸 、 potassium carbonate 、 1-羟基苯并三唑 、 magnesium 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸酐 、 N,N-二甲基甲酰胺 为溶剂， -30.0~20.0 ℃ 、393.01 kPa 条件下， 反应 61.16h， 生成 N-(5-(1-(4-nitrobenzyl)piperidin-4-yl)-2-isopropoxyphenyl)pyrazine-2-carboxamide
  参考文献：
  名称：

  Design, syntheses, and characterization of pharmacophore based chemokine receptor CCR5 antagonists as anti prostate cancer agents

  摘要：

  Accumulating evidence has shown multiple roles that chemokine receptor CCR5 may play to promote the progression of several types of cancer. The mechanism of such promotion is believed to involve chronic inflammation that creates a microenvironment which enhances tumor survival. Therefore, blocking CCR5 function with an antagonist may provide a novel treatment of cancers such as prostate cancer. Currently, several CCR5 antagonists are available, but all have been optimized for their inhibitory activity on HIV-1 cellular membrane invasion process rather than inhibition on cytoplasmic signaling pathways. Thus, there is need to develop CCR5 antagonists focusing on blockage of CCR5 downstream signaling and inhibition of CCR5 related prostate cancer proliferation and progression. In this report, a pharmacophore analysis was conducted based on docking studies of several known CCR5 antagonists in a CCR5 homology model. A unique structural skeleton for CCR5 antagonist was constructed and functionalized, resulting in a new series of small molecules to be synthesized and characterized. A combination of CCR5 calcium flux inhibition, anti prostate cancer cell proliferation, basal cytotoxicity, and in vivo animal model studies were applied to screen the newly synthesized compounds. Results from this study provided a potential lead compound for future CCR5 antagonist development focusing on prostate cancer therapy. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2013.09.004

文献信息

• Design, syntheses, and characterization of pharmacophore based chemokine receptor CCR5 antagonists as anti prostate cancer agents
  作者：Christopher K. Arnatt、Saheem A. Zaidi、Zhu Zhang、Guo Li、Amanda C. Richardson、Joy L. Ware、Yan Zhang

  DOI：10.1016/j.ejmech.2013.09.004

  日期：2013.11

  Accumulating evidence has shown multiple roles that chemokine receptor CCR5 may play to promote the progression of several types of cancer. The mechanism of such promotion is believed to involve chronic inflammation that creates a microenvironment which enhances tumor survival. Therefore, blocking CCR5 function with an antagonist may provide a novel treatment of cancers such as prostate cancer. Currently, several CCR5 antagonists are available, but all have been optimized for their inhibitory activity on HIV-1 cellular membrane invasion process rather than inhibition on cytoplasmic signaling pathways. Thus, there is need to develop CCR5 antagonists focusing on blockage of CCR5 downstream signaling and inhibition of CCR5 related prostate cancer proliferation and progression. In this report, a pharmacophore analysis was conducted based on docking studies of several known CCR5 antagonists in a CCR5 homology model. A unique structural skeleton for CCR5 antagonist was constructed and functionalized, resulting in a new series of small molecules to be synthesized and characterized. A combination of CCR5 calcium flux inhibition, anti prostate cancer cell proliferation, basal cytotoxicity, and in vivo animal model studies were applied to screen the newly synthesized compounds. Results from this study provided a potential lead compound for future CCR5 antagonist development focusing on prostate cancer therapy. Published by Elsevier Masson SAS.