N-((5-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)isooxazol-3-yl)methyl)acrylamide | 1328624-23-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-((5-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)isooxazol-3-yl)methyl)acrylamide
• 英文别名: N-((5-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)isoxazol-3-yl)methyl)acrylamide；N-[[5-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]pyrimidin-5-yl]-1,2-oxazol-3-yl]methyl]prop-2-enamide
• CAS: 1328624-23-2
• 化学式: C₂₃H₁₉ClN₆O₃
• 分子量: 462.895
• InChiKey: IONMHWXODSQZPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [3-氯-4-(吡啶-2-甲氧基)苯基]甲胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 吡啶 、 N-氯代丁二酰亚胺 、 四丁基氟化铵 、 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 45.17h， 生成 N-((5-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)isooxazol-3-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

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.