N-((2-(4-amino-6-(3-chloro-4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yloxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)-methyl)acrylamide | 1328624-02-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-((2-(4-amino-6-(3-chloro-4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yloxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)-methyl)acrylamide
• 英文别名: N-[[2-[4-amino-6-[3-chloro-4-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]oxyanilino]pyrimidin-5-yl]-1,3-oxazol-4-yl]methyl]prop-2-enamide
• CAS: 1328624-02-7
• 化学式: C₂₂H₁₈ClF₃N₈O₃
• 分子量: 534.885
• InChiKey: ZRZKVZZVULTROL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-((2-(4-amino-6-(3-chloro-4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yloxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)-methyl)acrylamide 、 乙酸酐 反应 2.0h， 以69%的产率得到N-((2-(4-acetamido-6-(3-chloro-4-(1-methyl-3-trifluoromethyl-1H-pyrazol-5-yloxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)methyl)acrylamide
  参考文献：
  名称：

  [EN] NOVEL PYRIMIDINE DERIVATIVE FOR INHIBITING THE GROWTH OF CANCER CELLS
  [FR] NOUVEAU DÉRIVÉ DE LA PYRIMIDINE POUR L'INHIBITION DE LA CROISSANCE DES CELLULES CANCÉREUSES

  摘要：

  公开号：

  WO2011099764A3
• 作为产物：
  描述：

  4,6-二氯-5-嘧啶甲醛 在 盐酸 、 lithium aluminium tetrahydride 、 sodium azide 、 磺酰氯 、 偶氮二异丁腈 、 三氯溴甲烷 、 二乙胺基三氟化硫 、 氨 、 水 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 四氯化碳 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 7.5h， 生成 N-((2-(4-amino-6-(3-chloro-4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yloxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)-methyl)acrylamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Pyrimidine-Based Dual Inhibitors of Human Epidermal Growth Factor Receptor 1 (HER-1) and HER-2 Tyrosine Kinases

  摘要：

  A novel series of N-4-(3-chlorophenyl)-5-(oxazol-2-yl)pyrimidine-4,6-diamines were synthesized and evaluated as dual inhibitors of HER-1/HER-2 tyrosine kinases. In contrast to the currently approved HER-2-targeted agent (lapatinib, 1), our irreversible HER-1/HER-2 inhibitors have the potential to overcome the clinically relevant and mutation-induced drug resistance. The selected compound (19a) showed excellent inhibitory activity toward HER-1/HER-2 tyrosine lcinases with selectivity over 20 other kinases and inhibited the proliferation of both cancer cell types: lapatinib-sensitive cell lines (SK-Br3, MDA-MB-175, and N87) and lapatinib-resistant cell lines (MDA-MB-453, H1781, and H1975). The excellent pharmacokinetic profiles of 19a in mice and rats led us to further investigation of a novel therapeutic agent for HER-2-targeting treatment of solid tumors, especially HER-2-positive breast/gastric cancer and HER-2-mutated lung cancer.

  DOI：

  10.1021/jm201758g

文献信息

• Synthesis and Biological Evaluation of Pyrimidine-Based Dual Inhibitors of Human Epidermal Growth Factor Receptor 1 (HER-1) and HER-2 Tyrosine Kinases
  作者：Mi Young Cha、Kwang-Ok Lee、Seok-Jong Kang、Young Hee Jung、Ji Yeon Song、Kyung Jin Choi、Joo Yun Byun、Han-Jae Lee、Gwan Sun Lee、Seung Bum Park、Maeng Sup Kim

  DOI：10.1021/jm201758g

  日期：2012.3.22

  A novel series of N-4-(3-chlorophenyl)-5-(oxazol-2-yl)pyrimidine-4,6-diamines were synthesized and evaluated as dual inhibitors of HER-1/HER-2 tyrosine kinases. In contrast to the currently approved HER-2-targeted agent (lapatinib, 1), our irreversible HER-1/HER-2 inhibitors have the potential to overcome the clinically relevant and mutation-induced drug resistance. The selected compound (19a) showed excellent inhibitory activity toward HER-1/HER-2 tyrosine lcinases with selectivity over 20 other kinases and inhibited the proliferation of both cancer cell types: lapatinib-sensitive cell lines (SK-Br3, MDA-MB-175, and N87) and lapatinib-resistant cell lines (MDA-MB-453, H1781, and H1975). The excellent pharmacokinetic profiles of 19a in mice and rats led us to further investigation of a novel therapeutic agent for HER-2-targeting treatment of solid tumors, especially HER-2-positive breast/gastric cancer and HER-2-mutated lung cancer.
• [EN] NOVEL PYRIMIDINE DERIVATIVE FOR INHIBITING THE GROWTH OF CANCER CELLS<br/>[FR] NOUVEAU DÉRIVÉ DE LA PYRIMIDINE POUR L'INHIBITION DE LA CROISSANCE DES CELLULES CANCÉREUSES
  申请人：HANMI HOLDINGS CO LTD

  公开号：WO2011099764A3

  公开（公告）日：2012-01-05