2-[(2-chloro-5-cyano-pyrimidin-4-yl)amino]benzamide

• 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: 2-[(2-chloro-5-cyano-pyrimidin-4-yl)amino]benzamide
• 英文别名: 2-[(2-Chloro-5-cyanopyrimidin-4-yl)amino]benzamide；2-[(2-chloro-5-cyanopyrimidin-4-yl)amino]benzamide
• 化学式: C₁₂H₈ClN₅O
• 分子量: 273.681
• InChiKey: QUKFJIYFFNWKRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-甲基-4-(4-甲基-1-哌嗪)苯胺 、 2-[(2-chloro-5-cyano-pyrimidin-4-yl)amino]benzamide 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以25%的产率得到2-[[5-cyano-2-[3-methyl-4-(4-methylpiperazin-1-yl)aniline]pyrimidin-4-yl]amino]benzamide
  参考文献：
  名称：

  Evaluation of the anti-malarial activity and cytotoxicity of 2,4-diamino-pyrimidine-based kinase inhibitors

  摘要：

  A series of 2,4 diamino-pyrimidines have been identified from an analysis of open access high throughput anti-malarial screening data reported by GlaxoSmithKline at the 3D7 and resistant Dd2 strains. SAR expansion has been performed using structural knowledge of the most plausible parasite target. Seventeen new analogs have been synthesized and tested against the resistant K1 strain of Plasmodium falciparum (Pf). The cytotoxicity of the compounds was assessed in Vero and A549 cells and their selectivity towards human kinases including JAK2 and EGFR were undertaken. We identified compound 5n and 5m as sub-micromolar inhibitors, with equivalent anti-malarial activity to Chloroquine (CQ). Compounds 5d and 5k, mu M inhibitors of Pf, displayed improved cytotoxicity with weak inhibition of the human kinases. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.08.055
• 作为产物：
  描述：

  2-氨基苯甲酰胺 、 2,4-二氯-5-氰基嘧啶 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 以41%的产率得到2-[(2-chloro-5-cyano-pyrimidin-4-yl)amino]benzamide
  参考文献：
  名称：

  Evaluation of the anti-malarial activity and cytotoxicity of 2,4-diamino-pyrimidine-based kinase inhibitors

  摘要：

  A series of 2,4 diamino-pyrimidines have been identified from an analysis of open access high throughput anti-malarial screening data reported by GlaxoSmithKline at the 3D7 and resistant Dd2 strains. SAR expansion has been performed using structural knowledge of the most plausible parasite target. Seventeen new analogs have been synthesized and tested against the resistant K1 strain of Plasmodium falciparum (Pf). The cytotoxicity of the compounds was assessed in Vero and A549 cells and their selectivity towards human kinases including JAK2 and EGFR were undertaken. We identified compound 5n and 5m as sub-micromolar inhibitors, with equivalent anti-malarial activity to Chloroquine (CQ). Compounds 5d and 5k, mu M inhibitors of Pf, displayed improved cytotoxicity with weak inhibition of the human kinases. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.08.055

文献信息

• ANTHRANILAMIDE INHIBITORS OF AURORA KINASE
  申请人：Johnson Neil W.

  公开号：US20080182852A1

  公开（公告）日：2008-07-31

  The present invention relates to a compound represented by the following formula: or a pharmaceutically acceptable salt thereof; where R 1 , R 2 , R 3 , R 4 , r and s are as previously defined. Compounds of the present invention are useful in the treatment of diseases associated with Aurora kinase activity such as cancer.

  本发明涉及以下公式所代表的化合物： 或其药学上可接受的盐； 其中R1、R2、R3、R4、r和s如前所定义。本发明的化合物在治疗与Aurora激酶活性相关的疾病，如癌症方面是有用的。
• US7625903B2
  申请人：——

  公开号：US7625903B2

  公开（公告）日：2009-12-01
• US7884098B2
  申请人：——

  公开号：US7884098B2

  公开（公告）日：2011-02-08
• [EN] ANTHRANILAMIDE INHIBITORS OF AURORA KINASE<br/>[FR] INHIBITEURS À L'ANTHRANILAMIDE DE L'AURORA KINASE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2008092049A1

  公开（公告）日：2008-07-31

  [EN] The present invention relates to a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof; where R¹, R², R³, R⁴, r and s are as previously defined. Compounds of the present invention are useful in the treatment of diseases associated with Aurora kinase activity such as cancer.
  [FR] Cette invention a trait à un composé de formule (I) suivante ou un de ses sels pharmaceutiquement acceptables, dans laquelle R¹, R², R³, R⁴, r et s sont tels que définis précédemment. Les composés de l'invention sont utilisés dans le traitement des maladies associées avec l'activité des Aurora kinases comme le cancer.
• Evaluation of the anti-malarial activity and cytotoxicity of 2,4-diamino-pyrimidine-based kinase inhibitors
  作者：Oraphan Phuangsawai、Paul Beswick、Siriluk Ratanabunyong、Lueacha Tabtimmai、Praphasri Suphakun、Phongphat Obounchoey、Pimonwan Srisook、Natharinee Horata、Irina Chuckowree、Supa Hannongbua、Simon E. Ward、Kiattawee Choowongkomon、M. Paul Gleeson

  DOI：10.1016/j.ejmech.2016.08.055

  日期：2016.11

  A series of 2,4 diamino-pyrimidines have been identified from an analysis of open access high throughput anti-malarial screening data reported by GlaxoSmithKline at the 3D7 and resistant Dd2 strains. SAR expansion has been performed using structural knowledge of the most plausible parasite target. Seventeen new analogs have been synthesized and tested against the resistant K1 strain of Plasmodium falciparum (Pf). The cytotoxicity of the compounds was assessed in Vero and A549 cells and their selectivity towards human kinases including JAK2 and EGFR were undertaken. We identified compound 5n and 5m as sub-micromolar inhibitors, with equivalent anti-malarial activity to Chloroquine (CQ). Compounds 5d and 5k, mu M inhibitors of Pf, displayed improved cytotoxicity with weak inhibition of the human kinases. (C) 2016 Elsevier Masson SAS. All rights reserved.