N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-iodo-6-methylpyrimidin-4-amine | 912354-47-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-iodo-6-methylpyrimidin-4-amine
• 英文别名: N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-5-iodo-6-methylpyrimidin-4-amine
• CAS: 912354-47-3
• 化学式: C₁₈H₁₄ClFIN₃O
• 分子量: 469.685
• InChiKey: VOCMESUITCHKHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-iodo-6-methylpyrimidin-4-amine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 sodium acetate 作用下， 以 N-甲基吡咯烷酮 、 甲苯 为溶剂， 反应 7.0h， 生成 N-(3-(-2-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-methylpyrimidin-5-yl)vinyl)phenyl)-4-(dimethylamino)but-2-enamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors

  摘要：

  36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values <1 mu M for EGFR and <5 mu M for A-549 and HL60 cells growth inhibition. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.053
• 作为产物：
  描述：

  4-羟基-6-甲基嘧啶 在 甲烷磺酸 、 碘 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 二乙二醇二甲醚 、 水 为溶剂， 反应 7.0h， 生成 N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-iodo-6-methylpyrimidin-4-amine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors

  摘要：

  36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values <1 mu M for EGFR and <5 mu M for A-549 and HL60 cells growth inhibition. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.053

文献信息

• Synthesis and evaluation of novel pyrimidine-based dual EGFR/Her-2 inhibitors
  作者：Naoyuki Suzuki、Takeshi Shiota、Fumihiko Watanabe、Norihiro Haga、Takami Murashi、Takafumi Ohara、Kenji Matsuo、Naoki Oomori、Hiroshi Yari、Keiji Dohi、Makiko Inoue、Motofumi Iguchi、Jyunko Sentou、Tooru Wada

  DOI：10.1016/j.bmcl.2011.01.119

  日期：2011.3

  A structure-activity relationship study of 4-anilinopyrimidines for dual EGFR/Her-2 inhibitor has resulted in the identification of 4-anilino-5-alkenyl or 5-alkynyl-6-methylpyrimidine derivatives that have exhibited effective inhibitory activity against both enzymes. The presence of 5-alkenyl or 5-alkynyl moiety bearing terminal hydrophilic group played important role for inhibition of these enzymes. Selected compounds in the series demonstrated some activity against Her-2 dependent cell line ( BT474). (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases
  作者：Naoyuki Suzuki、Takeshi Shiota、Fumihiko Watanabe、Norihiro Haga、Takami Murashi、Takafumi Ohara、Kenji Matsuo、Naoki Omori、Hiroshi Yari、Keiji Dohi、Makiko Inoue、Motofumi Iguchi、Jyunko Sentou、Tooru Wada

  DOI：10.1016/j.bmcl.2011.10.103

  日期：2012.1

  5-Alkenyl or 5-alkynyl-4-anilinopyrimidines were prepared and evaluated for in vitro inhibition of EGFR/Her-2 kinase activity and the growth of tumor cell lines (BT474 and N87). Several of these compounds inhibited the growth of BT474 and N87 at concentrations below 200 nM. Structure-activity relationship studies revealed a critical role for the 5-alkynyl moieties. The representative compound 19 exhibited significant antitumor potency in a mouse xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.