N-tert-butyl-3-(5-cyano-2-(3-methyl-4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide

• 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: N-tert-butyl-3-(5-cyano-2-(3-methyl-4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide
• 英文别名: N-tert-butyl-3-[[5-cyano-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]benzenesulfonamide
• 化学式: C₂₇H₃₄N₈O₂S
• 分子量: 534.685
• InChiKey: BSPOXGNPEWSHFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-氟-5-硝基甲苯 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 N-tert-butyl-3-(5-cyano-2-(3-methyl-4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide
  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

• 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.