2,4-diamino-5-<3,5-dimethoxy-4-<3-(N-(4-toluenesulfonyl)-4'-trifluoromethylanilino)propoxy>benzyl>pyrimidine | 172797-85-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4-diamino-5-<3,5-dimethoxy-4-<3-(N-(4-toluenesulfonyl)-4'-trifluoromethylanilino)propoxy>benzyl>pyrimidine
• 英文别名: N-[3-[4-[(2,4-diaminopyrimidin-5-yl)methyl]-2,6-dimethoxyphenoxy]propyl]-4-methyl-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide
• CAS: 172797-85-2
• 化学式: C₃₀H₃₂F₃N₅O₅S
• 分子量: 631.676
• InChiKey: MKIQUUGZQNMQOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-<3,5-dimethoxy-4-<3-(N-(4-toluenesulfonyl)-4'-trifluoromethylanilino)propoxy>benzyl>pyrimidine 在 氨 、 lithium 作用下， 以19%的产率得到2,4-diamino-5-<3,5-dimethoxy-4-<3-(4'-methylanilino)propoxy>benzyl>pyrimidine
  参考文献：
  名称：

  New benzylpyrimidines: inhibition of DHFR from various species. QSAR, CoMFA and PC analysis

  摘要：

  To further analyze the structural requirements responsible for the enhanced activity of the newly developed, highly active benzylpyrimidine K-130, a series of trimethoprim analogues with various 4-anilinoalkoxy moieties has been synthesized and tested against dihydrofolate reductase (DHFR) derived from various species (Mycobacterium lufu, Escherichia coli, Candida albicans and rats). The importance of the secondary amino group for binding affinity could be shown by varying the substituent in the para position to the sec-amino moiety. This finding could be supported by multiple linear regression and comparative molecular field analysis (CoMFA). The polarized SO2, group, which was thought to be responsible for the increased activity of K-130, seems not to be the only group Important for receptor binding. Additionally, a high selectivity of the new compounds for DHFR derived from the various bacteria and C albicans compared with DHFR derived from rat liver is shown by PC analysis.

  DOI：

  10.1016/0223-5234(96)88297-3
• 作为产物：
  描述：

  2,4-diamino-5-(3,5-dimethoxy-4-hydroxybenzyl)pyrimidine 在 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.15h， 生成 2,4-diamino-5-<3,5-dimethoxy-4-<3-(N-(4-toluenesulfonyl)-4'-trifluoromethylanilino)propoxy>benzyl>pyrimidine
  参考文献：
  名称：

  New benzylpyrimidines: inhibition of DHFR from various species. QSAR, CoMFA and PC analysis

  摘要：

  To further analyze the structural requirements responsible for the enhanced activity of the newly developed, highly active benzylpyrimidine K-130, a series of trimethoprim analogues with various 4-anilinoalkoxy moieties has been synthesized and tested against dihydrofolate reductase (DHFR) derived from various species (Mycobacterium lufu, Escherichia coli, Candida albicans and rats). The importance of the secondary amino group for binding affinity could be shown by varying the substituent in the para position to the sec-amino moiety. This finding could be supported by multiple linear regression and comparative molecular field analysis (CoMFA). The polarized SO2, group, which was thought to be responsible for the increased activity of K-130, seems not to be the only group Important for receptor binding. Additionally, a high selectivity of the new compounds for DHFR derived from the various bacteria and C albicans compared with DHFR derived from rat liver is shown by PC analysis.

  DOI：

  10.1016/0223-5234(96)88297-3

文献信息

• New benzylpyrimidines: inhibition of DHFR from various species. QSAR, CoMFA and PC analysis
  作者：K-H Czaplinski、W Hänsel、M Wiese、JK Seydel

  DOI：10.1016/0223-5234(96)88297-3

  日期：1995.1

  To further analyze the structural requirements responsible for the enhanced activity of the newly developed, highly active benzylpyrimidine K-130, a series of trimethoprim analogues with various 4-anilinoalkoxy moieties has been synthesized and tested against dihydrofolate reductase (DHFR) derived from various species (Mycobacterium lufu, Escherichia coli, Candida albicans and rats). The importance of the secondary amino group for binding affinity could be shown by varying the substituent in the para position to the sec-amino moiety. This finding could be supported by multiple linear regression and comparative molecular field analysis (CoMFA). The polarized SO2, group, which was thought to be responsible for the increased activity of K-130, seems not to be the only group Important for receptor binding. Additionally, a high selectivity of the new compounds for DHFR derived from the various bacteria and C albicans compared with DHFR derived from rat liver is shown by PC analysis.