5-(4-aminomethyloxazol-2-yl)-N(4)-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrimidin-4,6-diamine | 1328623-74-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-aminomethyloxazol-2-yl)-N(4)-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrimidin-4,6-diamine
• 英文别名: 5-[4-(aminomethyl)-1,3-oxazol-2-yl]-4-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]pyrimidine-4,6-diamine
• CAS: 1328623-74-0
• 化学式: C₂₀H₁₈ClN₇O₂
• 分子量: 423.862
• InChiKey: IJAWNMULMLJYAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  138
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-(4-aminomethyloxazol-2-yl)-N(4)-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrimidin-4,6-diamine 在 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.17h， 生成 N-((2-(4-acetamido-6-(3-chloro-4-(pyridin-2-ylmethoxy)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：

  5-(4-(aminomethyl)oxazol-2-yl)-N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrimidin-4,6-diamine 在 水 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以50 mg的产率得到5-(4-aminomethyloxazol-2-yl)-N(4)-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)pyrimidin-4,6-diamine
  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