(2-(4-amino-6-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)methanol | 1364411-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2-(4-amino-6-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)methanol
• 英文别名: (2-(4-amino-6-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)ooxazol-4-yl)methanol；[2-[4-Amino-6-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]pyrimidin-5-yl]-1,3-oxazol-4-yl]methanol
• CAS: 1364411-02-8
• 化学式: C₂₀H₁₇ClN₆O₃
• 分子量: 424.846
• InChiKey: UVVADUCAKJJDQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：
  132
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2-(4-amino-6-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)methanol 在 sodium azide 、 三苯基膦 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 5-(4-(aminomethyl)oxazol-2-yl)-N4-(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
• 作为产物：
  描述：

  methyl 2-(4,6-dichloropyrimidin-5-carboxamido)-3-hydroxypropanoate 在 盐酸 、 lithium aluminium tetrahydride 、 三氯溴甲烷 、 二乙胺基三氟化硫 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 叔丁醇 为溶剂， 反应 10.33h， 生成 (2-(4-amino-6-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)oxazol-4-yl)methanol
  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

• [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