4-Chloro-5-ethynyl-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]pyrrolo[2,3-d]pyrimidin-2-amine | 1394818-95-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-Chloro-5-ethynyl-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]pyrrolo[2,3-d]pyrimidin-2-amine
• 英文别名: 4-chloro-5-ethynyl-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]pyrrolo[2,3-d]pyrimidin-2-amine
• CAS: 1394818-95-1
• 化学式: C₁₇H₁₆ClN₅O
• 分子量: 341.8
• InChiKey: KZFNSFSFTNJMTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-5-碘-7-(4-甲氧基-3,5-二甲基吡啶-2-甲基)-7H-吡咯并[2,3-d]嘧啶-2-胺 在 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 3.5h， 生成 4-Chloro-5-ethynyl-7-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  EC144 Is a Potent Inhibitor of the Heat Shock Protein 90

  摘要：

  Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90 alpha binding assay (IC50 = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC50 = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

  DOI：

  10.1021/jm300810x

文献信息

• EC144 Is a Potent Inhibitor of the Heat Shock Protein 90
  作者：Jiandong Shi、Ryan Van de Water、Kevin Hong、Ryan B. Lamer、Kenneth W. Weichert、Cristina M. Sandoval、Srinivas R. Kasibhatla、Marcus F. Boehm、Jianhua Chao、Karen Lundgren、Noelito Timple、Rachel Lough、Gerardo Ibanez、Christina Boykin、Francis J. Burrows、Marilyn R. Kehry、Theodore J. Yun、Erin K. Harning、Christine Ambrose、Jeffrey Thompson、Sarah A. Bixler、Anthone Dunah、Pamela Snodgrass-Belt、Joseph Arndt、Istvan J. Enyedy、Ping Li、Victor S. Hong、Andres McKenzie、Marco A. Biamonte

  DOI：10.1021/jm300810x

  日期：2012.9.13

  Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90 alpha binding assay (IC50 = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC50 = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.