4-(2-(4-(3-((3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)amino)-3-oxopropyl)piperazin-1-yl)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1588522-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(2-(4-(3-((3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)amino)-3-oxopropyl)piperazin-1-yl)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
• 英文别名: 3-[4-[2-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]ethyl]piperazin-1-yl]-N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]propanamide
• CAS: 1588522-96-6
• 化学式: C₃₉H₄₅ClN₁₀O₈S
• 分子量: 849.367
• InChiKey: UZLAZBPSXWZCAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  59
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  202
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  5-氟-2-硝基苯酚 在 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 丙酮 、 仲丁醇 为溶剂， 反应 18.0h， 生成 4-(2-(4-(3-((3-((5-chloro-2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)amino)-3-oxopropyl)piperazin-1-yl)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors

  摘要：

  Novel compounds 12a-i were synthesized and biologically evaluated. Several ones exhibited stronger inhibitory activity than gefitinib against EGFR L858R/T790M and antiproliferative effects on H1975 and HCC827 cells. The 3-aminopropamide in compounds like 12h could be converted to the active acrylamide in the presence of arginine. Importantly, 12h showed improved stability relative to compound 1 whose structure is same to 12h excepting an acrylamide moiety. Interestingly, 12i, a NO donating compound of 12h, showed more potent and selective inhibition than 12h on H1975 cells. Significantly, 12i produced high levels of NO in H1975 cells but not in non-tumorous 16HBE cells, and its inhibition was diminished by NO scavenger. Furthermore, 12i dose-dependently produced inhibitory effects on EGFR downstream signaling in H1975 cells. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.02.032

文献信息

• Synthesis and evaluation of 2-anilinopyrimidines bearing 3-aminopropamides as potential epidermal growth factor receptor inhibitors
  作者：Chun Han、Ledong Wan、Hongbin Ji、Ke Ding、Zhangjian Huang、Yisheng Lai、Sixun Peng、Yihua Zhang

  DOI：10.1016/j.ejmech.2014.02.032

  日期：2014.4

  Novel compounds 12a-i were synthesized and biologically evaluated. Several ones exhibited stronger inhibitory activity than gefitinib against EGFR L858R/T790M and antiproliferative effects on H1975 and HCC827 cells. The 3-aminopropamide in compounds like 12h could be converted to the active acrylamide in the presence of arginine. Importantly, 12h showed improved stability relative to compound 1 whose structure is same to 12h excepting an acrylamide moiety. Interestingly, 12i, a NO donating compound of 12h, showed more potent and selective inhibition than 12h on H1975 cells. Significantly, 12i produced high levels of NO in H1975 cells but not in non-tumorous 16HBE cells, and its inhibition was diminished by NO scavenger. Furthermore, 12i dose-dependently produced inhibitory effects on EGFR downstream signaling in H1975 cells. (c) 2014 Elsevier Masson SAS. All rights reserved.