2-chloro-4-(2-chlorophenoxy)pyrimidine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-(2-chlorophenoxy)pyrimidine
• 化学式: C₁₀H₆Cl₂N₂O
• 分子量: 241.076
• InChiKey: QVCHGAXPMISGPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(2-chlorophenoxy)pyrimidine 在 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Anticancer activity evaluation of indazolyl-substituted piperidin-4-yl-aminopyrimidines

  摘要：

  Based on our previous work, a series of indazolyl-substituted piperidin-4-yl-aminopyrimidines, which were firstly used as anti-HIV agents, were evaluated for their anticancer potency in five cancer cell lines. Notably, they exhibited excellent activities with IC50 values ranging from 2.29 to 22.89 mu M in H1975 cells, among which 6c-e displayed lower cytotoxicity to normal lung cells than gefitinib. Furthermore, the typical compound 6e, which was fourfold more potent than gefitinib in H1975 cell line, was tested for its ability to inhibit H1975 cell migration. The results revealed that 6e showed superior anti-migration activity to gefitinib. In order to investigate the cytotoxicity of 6e in H1975 cells, AO/EB staining experiment was carried out and the results indicated 6e could induce cell apoptosis in a concentration-dependent manner. It is worth noting that comparing with first-generation EGFR inhibitors this series of compounds showed better anti-mutation activity, even if they lack acrylamide moiety which is regarded as necessary for anti-mutation potency in second or third-generation inhibitors. These findings indicate that it might be a new concept to explore noncovalent and high-affinity inhibitors with excellent anti-mutation potency.

  DOI：

  10.1007/s00044-020-02531-6
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 邻氯苯酚 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-chloro-4-(2-chlorophenoxy)pyrimidine
  参考文献：
  名称：

  地拉韦啶和哌啶-4-基-氨基嘧啶 (DPAPY) 的杂合体作为有效的 HIV-1 NNRTIs：设计、合成和生物活性

  摘要：

  地拉韦啶和哌啶-4-基-氨基嘧啶(DPAPY)杂合体是由两种优良的HIV-1 NNRTIs地拉韦啶和哌啶-4-基-氨基嘧啶通过分子杂交设计而成。制备了目标化合物4a-r，并评估了其细胞抗HIV活性和细胞毒性以及对HIV-1逆转录酶（RT）的抑制活性。所有新合成的化合物均表现出中等至优异的抗野生型 (WT) HIV-1 效力，EC 50值在 5.7 至 0.0086 μM 范围内，而对抗 RT，IC 50值在 12.0 至 0.11 μM 范围内，表明 DPAPY是特异性 RT 抑制剂。其中，4d显示出针对 WT HIV-1 的最有效活性（EC 50  = 8.6 nM，SI = 2151）。令人欣慰的是，它对单一 HIV-1 突变体 L100I、K103N、Y181C、Y188L、E138K 以及双突变体 F227L + V106A 表现出良好至优异的效力。此外，还总结了初步的构效关系，并

  DOI：

  10.1016/j.ejmech.2023.115114

文献信息

• Anticancer activity evaluation of indazolyl-substituted piperidin-4-yl-aminopyrimidines
  作者：Chao Wang、Xiao-Wen Liu、Ting Xiao、Zhi-Qiang Xu、Shuang Cao、Hai-Feng Wang、Qiong-Jiao Yan、Shuang-Xi Gu、Yuan-Yuan Zhu

  DOI：10.1007/s00044-020-02531-6

  日期：2020.5

  Based on our previous work, a series of indazolyl-substituted piperidin-4-yl-aminopyrimidines, which were firstly used as anti-HIV agents, were evaluated for their anticancer potency in five cancer cell lines. Notably, they exhibited excellent activities with IC50 values ranging from 2.29 to 22.89 mu M in H1975 cells, among which 6c-e displayed lower cytotoxicity to normal lung cells than gefitinib. Furthermore, the typical compound 6e, which was fourfold more potent than gefitinib in H1975 cell line, was tested for its ability to inhibit H1975 cell migration. The results revealed that 6e showed superior anti-migration activity to gefitinib. In order to investigate the cytotoxicity of 6e in H1975 cells, AO/EB staining experiment was carried out and the results indicated 6e could induce cell apoptosis in a concentration-dependent manner. It is worth noting that comparing with first-generation EGFR inhibitors this series of compounds showed better anti-mutation activity, even if they lack acrylamide moiety which is regarded as necessary for anti-mutation potency in second or third-generation inhibitors. These findings indicate that it might be a new concept to explore noncovalent and high-affinity inhibitors with excellent anti-mutation potency.
• JOJIMA TERUOMI; TAKESHIBA HIDEO; KINOTO TAKAO; KONDO YASUHIKO, ANNU. REPT. SANKYO RES. LAB., 1980, 32, 114-120
  作者：JOJIMA TERUOMI、 TAKESHIBA HIDEO、 KINOTO TAKAO、 KONDO YASUHIKO

  DOI：——

  日期：——
• Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities
  作者：Ting Xiao、Jia-Fan Tang、Ge Meng、Christophe Pannecouque、Yuan-Yuan Zhu、Gen-Yan Liu、Zhi-Qiang Xu、Feng-Shou Wu、Shuang-Xi Gu、Fen-Er Chen

  DOI：10.1016/j.ejmech.2019.111864

  日期：2020.1

  A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with ECK values ranging from 1.5 to 0.0064 mu M. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC50 = 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC50 = 0.077 mu M), Y181C (EC50 = 0.11 mu M), E138K (EC50 = 0.057 mu M), and moderate activity against double mutants RES056 (EC50 = 8.7 mu M). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Hybrids of delavirdine and piperdin-4-yl-aminopyrimidines (DPAPYs) as potent HIV-1 NNRTIs: Design, synthesis and biological activities
  作者：Wei Ming、Wen-Long Lu、Christophe Pannecouque、Jiong Chen、Hai-Feng Wang、Ya-Qi Xiao、Sha Hu、Shuang-Xi Gu、Yuan-Yuan Zhu、Fen-Er Chen

  DOI：10.1016/j.ejmech.2023.115114

  日期：2023.2

  excellent HIV-1 NNRTIs delavirdine and piperidin-4-yl-aminopyrimidine via molecular hybridization. The target compounds 4a-r were prepared and evaluated for their cellular anti-HIV activities and cytotoxicities as well as the inhibitory activities against HIV-1 reverse transcriptase (RT). All the newly synthesized compounds demonstrated moderate to excellent potency against wild-type (WT) HIV-1 with EC50

  地拉韦啶和哌啶-4-基-氨基嘧啶(DPAPY)杂合体是由两种优良的HIV-1 NNRTIs地拉韦啶和哌啶-4-基-氨基嘧啶通过分子杂交设计而成。制备了目标化合物4a-r，并评估了其细胞抗HIV活性和细胞毒性以及对HIV-1逆转录酶（RT）的抑制活性。所有新合成的化合物均表现出中等至优异的抗野生型 (WT) HIV-1 效力，EC 50值在 5.7 至 0.0086 μM 范围内，而对抗 RT，IC 50值在 12.0 至 0.11 μM 范围内，表明 DPAPY是特异性 RT 抑制剂。其中，4d显示出针对 WT HIV-1 的最有效活性（EC 50  = 8.6 nM，SI = 2151）。令人欣慰的是，它对单一 HIV-1 突变体 L100I、K103N、Y181C、Y188L、E138K 以及双突变体 F227L + V106A 表现出良好至优异的效力。此外，还总结了初步的构效关系，并