methyl 2-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)-4,5-dihydrooxazole-4-carboxylate | 1328624-11-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)-4,5-dihydrooxazole-4-carboxylate
• CAS: 1328624-11-8
• 化学式: C₂₁H₁₈ClN₅O₄
• 分子量: 439.858
• InChiKey: ZAUKNPIDIPRXPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  107.82
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)-4,5-dihydrooxazole-4-carboxylate 在 lithium aluminium tetrahydride 、 sodium azide 、 三氯溴甲烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-[4-(azidomethyl)-1,3-oxazol-2-yl]-N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]pyrimidin-4-amine
  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：

  ethyl 4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidine-5-carboxylate 在 二乙胺基三氟化硫 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)pyrimidin-5-yl)-4,5-dihydrooxazole-4-carboxylate
  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