4,6-diethoxy-N,N-bis(4-methoxybenzyl)pyrimidin-2-amine | 1268273-26-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4,6-diethoxy-N,N-bis(4-methoxybenzyl)pyrimidin-2-amine
• 英文别名: 5-iodo-4,6-diethoxy-N,N-bis(4-methoxybenzyl)pyrimidin-2-amine；4,6-diethoxy-5-iodo-N,N-bis[(4-methoxyphenyl)methyl]pyrimidin-2-amine
• CAS: 1268273-26-2
• 化学式: C₂₄H₂₈IN₃O₄
• 分子量: 549.409
• InChiKey: IIKQBXHXAIRMHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4,6-diethoxy-N,N-bis(4-methoxybenzyl)pyrimidin-2-amine 在 4-二甲氨基吡啶 、 copper(l) iodide 、 新铜试剂 、 potassium carbonate 、 氟化氢吡啶 、 三氟乙酸 、 sodium nitrite 作用下， 以 氯仿 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.0h， 生成 N,N′-(2-((4,6-diethoxy-2-(piperidin-1-yl)pyrimidin-5-yl)thio)pyrimidine-4,6-diyl)diacetamide
  参考文献：
  名称：

  Heat Shock Protein 70 Inhibitors. 1. 2,5′-Thiodipyrimidine and 5-(Phenylthio)pyrimidine Acrylamides as Irreversible Binders to an Allosteric Site on Heat Shock Protein 70

  摘要：

  Heat shock protein 70 (Hsp70) is an important emerging. cancer. target whose inhibition may affect multiple cancer-associated signaling pathways and, moreover, result in significant cancer cell apoptosis. Despite considerable interest from both academia and pharmaceutical companies in the discovery and development of druglike Hsp70 inhibitors, little success has been reported so far. Here we describe structure activity relationship studies in the first rationally designed Hsp70 inhibitor class that binds to a novel allosteric pocket located in the N-terminal domain of the protein. These 2,5'-thiodipyrimidine and 5-(phenylthio)-pyrimidine acrylamides take advantage of an active cysteine embedded in the allosteric pocket to act as covalent protein modifiers upon binding. The study identifies derivatives 17a and 20a, which selectively bind to Hsp70 in cancer cells. Addition of high nanomolar to low micromolar concentrations of these inhibitors to cancer cells leads to a reduction in the steady-state levels of Hsp70-sheltered oncoproteins, an effect associated with inhibition of cancer cell growth and apoptosis. In summary, the described scaffolds represent a viable starting point for the development of druglike Hsp70 inhibitors as novel anticancer therapeutics.

  DOI：

  10.1021/jm401551n
• 作为产物：
  描述：

  2-Amino-4,6-diethoxy-pyrimidin 在 N-碘代丁二酰亚胺 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.0h， 生成 4,6-diethoxy-N,N-bis(4-methoxybenzyl)pyrimidin-2-amine
  参考文献：
  名称：

  [EN] HEAT SHOCK PROTEIN BINDING COMPOUNDS, COMPOSITIONS, AND METHODS FOR MAKING AND USING SAME
  [FR] COMPOSÉS DE LIAISON À UNE PROTÉINE DE CHOC THERMIQUE, COMPOSITIONS ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER

  摘要：

  公开号：

  WO2011022440A9