(3,5-Dimethoxy-phenyl)-(6-methyl-2-pyridin-2-yl-pyrimidin-4-yl)-amine | 787542-15-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (3,5-Dimethoxy-phenyl)-(6-methyl-2-pyridin-2-yl-pyrimidin-4-yl)-amine
• 英文别名: N-(3,5-Dimethoxyphenyl)-6-methyl-2-(pyridin-2-yl)pyrimidin-4-amine；N-(3,5-dimethoxyphenyl)-6-methyl-2-pyridin-2-ylpyrimidin-4-amine
• CAS: 787542-15-8
• 化学式: C₁₈H₁₈N₄O₂
• 分子量: 322.367
• InChiKey: JBOGIPYKAQAOQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-6-甲基-2-(2-吡啶)嘧啶 、 3,5-二甲氧基苯胺 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以26%的产率得到(3,5-Dimethoxy-phenyl)-(6-methyl-2-pyridin-2-yl-pyrimidin-4-yl)-amine
  参考文献：
  名称：

  Discovery of substituted 4-anilino-2-(2-pyridyl)pyrimidines as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. Part 1: Structure–activity relationships of the 4-anilino group

  摘要：

  A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS assay. Compound 5a was found to arrest T47D cells in G(2)/M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta-position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (5a) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (51), was obtained through the SAR studies. Compound 51 is highly active with an EC50 value of 18 nM in the caspase activation assay in T47D breast cells. Interestingly, 5a and other meta-mono-substituted compounds were active against T47D cells but were not active against H 1299 and HT29 cells, while 51 and other 2,5-disubstituted compounds were active against all the three cells. In a tubulin polymerization assay, compound 51 inhibited tubulin polymerization with an IC50 value of < 0.5 mu M while 5a was not active up to 50 mu M. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.08.002

文献信息

• Discovery of substituted 4-anilino-2-(2-pyridyl)pyrimidines as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. Part 1: Structure–activity relationships of the 4-anilino group
  作者：Nilantha Sirisoma、Shailaja Kasibhatla、Bao Nguyen、Azra Pervin、Yang Wang、Gisela Claassen、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1016/j.bmc.2006.08.002

  日期：2006.12

  A series of 4-anilino-2-(2-pyridyl)pyrimidines has been discovered as a new class of potent inducers of apoptosis using a cell-based HTS assay. Compound 5a was found to arrest T47D cells in G(2)/M and induced apoptosis. SAR studies showed that a small and electron-donating group at the meta-position of the anilino ring is important for activity. A 20-fold increase in potency, from hit compound 4-(3-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (5a) to lead compound 4-(2,5-dimethoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (51), was obtained through the SAR studies. Compound 51 is highly active with an EC50 value of 18 nM in the caspase activation assay in T47D breast cells. Interestingly, 5a and other meta-mono-substituted compounds were active against T47D cells but were not active against H 1299 and HT29 cells, while 51 and other 2,5-disubstituted compounds were active against all the three cells. In a tubulin polymerization assay, compound 51 inhibited tubulin polymerization with an IC50 value of < 0.5 mu M while 5a was not active up to 50 mu M. (c) 2006 Elsevier Ltd. All rights reserved.