4-(4-methylpiperazin-1-ylcarbonyl)phenylisocyanate | 1350767-53-1

• 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: 4-(4-methylpiperazin-1-ylcarbonyl)phenylisocyanate
• 英文别名: (4-Isocyanatophenyl)-(4-methylpiperazin-1-yl)methanone；(4-isocyanatophenyl)-(4-methylpiperazin-1-yl)methanone
• CAS: 1350767-53-1
• 化学式: C₁₃H₁₅N₃O₂
• 分子量: 245.281
• InChiKey: JVXKFDHFJDTYLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N⁴-(3-ethynylphenyl)quinazoline-4,6-diamine 、 4-(4-methylpiperazin-1-ylcarbonyl)phenylisocyanate 以 甲苯 为溶剂， 反应 2.0h， 生成 1-(4-((3-ethynylphenyl)amino)quinazolin-6-yl)-3-(4-(4-methylpiperazin-1-carbonyl)phenyl)urea
  参考文献：
  名称：

  Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents

  摘要：

  In present study, 4-anilinoquinazolines scaffold, arylurea and tertiary amine moiety were combined to design, synthesize gefitinib analogs and discover novel anticancer agents. A series of 4-anilinoquinazoline derivatives (1, 2, 3 and 4) bearing arylurea and tertiary amine moiety at its 6-position were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against A431 cell and A549 cell. The SAR of the title compounds was discussed. The compounds 2d, 2i and 2j with potent antiproliferative activities were evaluated their inhibitory activity against EGFR-TK. Compound 2j displayed potent inhibitory activity against EGFR-TK. In addition, compound 2j, at 50 mg/kg, can completely inhibit cancer growth in established nude mouse A549 xenograft model in vivo. These results suggest that the 4-anilinoquinazoline derivatives bearing diarylurea and tertiary amino moiety at its 6-position can serve as anticancer agents and EGFR inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.001
• 作为产物：
  描述：

  对苯二甲酸单甲酯 在 氯化亚砜 、 草酰氯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 4-(4-methylpiperazin-1-ylcarbonyl)phenylisocyanate
  参考文献：
  名称：

  具有4-甲基哌嗪基羰基部分的二芳基脲衍生物的合成和细胞毒活性

  摘要：

  通过异氰酸酯与芳基胺的反应合成了11个带有N-甲基哌嗪基部分的二芳基脲衍生物（1a-1k）。1a–1k的结构通过1 H-NMR和MS表征。通过MTT方法评估了1a-1k的细胞毒性活性对人肺腺癌上皮细胞系A549和人前列腺癌细胞系PC3的影响。化合物1d和1k显示出强大的细胞毒活性。结果表明，活性与另一个苯环上的取代基有很大关系。

  DOI：

  10.1007/s00044-012-0398-y

文献信息

• mTOR SELECTIVE KINASE INHIBITORS
  申请人：Liang Congxin

  公开号：US20130072481A1

  公开（公告）日：2013-03-21

  The 4-urea-phenyl substituted 6-morpholin-4-yl-pyrazolo[3,4-d]pyrimidine derivatives are potent and selective inhibitors of mTOR kinase and are useful in treating disorders related to abnormal mTOR activities such as cancer, immune disorders, cardiovascular disease, ocular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders.

  4-脲基苯基取代的6-吗啉-4-基吡唑并[3,4-d]嘧啶衍生物是 mTOR 激酶的有效且选择性抑制剂，可用于治疗与异常 mTOR 活性相关的疾病，如癌症、免疫紊乱、心血管疾病、眼部疾病、病毒感染、炎症、代谢/内分泌紊乱和神经系统疾病。
• Synthesis and cytotoxic activity of diaryl urea derivatives with a 4-methylpiperazinylcarbonyl moiety
  作者：Wei Xuan、Wen Ding、Hong-xiang Hui、San-qi Zhang

  DOI：10.1007/s00044-012-0398-y

  日期：2013.8

  reaction of isocyanate with arylamine. The structures of 1a–1k were characterized by 1H-NMR and MS. The cytotoxic activities of 1a–1k were evaluated via MTT method against human lung adenocarcinoma epithelial cell line A549 and human prostate carcinoma cell line PC3. Compounds 1d and 1k displayed potent cytotoxic activity. The results suggested that the activities are considerably related to the substituent

  通过异氰酸酯与芳基胺的反应合成了11个带有N-甲基哌嗪基部分的二芳基脲衍生物（1a-1k）。1a–1k的结构通过1 H-NMR和MS表征。通过MTT方法评估了1a-1k的细胞毒性活性对人肺腺癌上皮细胞系A549和人前列腺癌细胞系PC3的影响。化合物1d和1k显示出强大的细胞毒活性。结果表明，活性与另一个苯环上的取代基有很大关系。
• Discovery of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-ones as novel EGFR inhibitor by scaffold hopping
  作者：Bo-Rui Kang、Ai-Lin Shan、Yi-Ping Li、Jing Xu、She-Min Lu、San-Qi Zhang

  DOI：10.1016/j.bmc.2013.09.027

  日期：2013.11

  2-Aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one has been proposed as a novel scaffold of EGFR inhibitor based on scaffold hoping. In the present study, a series of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one derivatives were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against two human cancer cell lines, including A431 and A549. The SAR of the title compounds was preliminarily discussed. The compounds with ideal inhibition were evaluated through ELISA-based EGFR-TK assay. Compound 6c showed the best activity against A431 and EGFR tyrosine kinase. These findings suggest that title compounds are EGFR inhibitors with novel structures. (C) 2013 Elsevier Ltd. All rights reserved.
• US8912178B2
  申请人：——

  公开号：US8912178B2

  公开（公告）日：2014-12-16
• Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents
  作者：Sai-Jie Zuo、Sai Zhang、Shuai Mao、Xiao-Xiao Xie、Xue Xiao、Min-Hnag Xin、Wei Xuan、Yuan-Yuan He、Yong-Xiao Cao、San-Qi Zhang

  DOI：10.1016/j.bmc.2015.12.001

  日期：2016.1

  In present study, 4-anilinoquinazolines scaffold, arylurea and tertiary amine moiety were combined to design, synthesize gefitinib analogs and discover novel anticancer agents. A series of 4-anilinoquinazoline derivatives (1, 2, 3 and 4) bearing arylurea and tertiary amine moiety at its 6-position were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against A431 cell and A549 cell. The SAR of the title compounds was discussed. The compounds 2d, 2i and 2j with potent antiproliferative activities were evaluated their inhibitory activity against EGFR-TK. Compound 2j displayed potent inhibitory activity against EGFR-TK. In addition, compound 2j, at 50 mg/kg, can completely inhibit cancer growth in established nude mouse A549 xenograft model in vivo. These results suggest that the 4-anilinoquinazoline derivatives bearing diarylurea and tertiary amino moiety at its 6-position can serve as anticancer agents and EGFR inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.