6-chloro-2,4-diamino-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine | 130985-30-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 6-chloro-2,4-diamino-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine
• 英文别名: 6-chloro-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine-2,4-diamine
• CAS: 130985-30-7
• 化学式: C₁₅H₁₇ClN₄O₂
• 分子量: 320.779
• InChiKey: ZJBONQFHVPMYDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96.28
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  6-chloro-2,4-diamino-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 以34%的产率得到2,4-diamino-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogs of trimethoprim

  摘要：

  A conformationally restricted analogue of trimethoprim (1a) has been prepared by connecting the ortho position of the benzene ring to the methylene linkage with two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry involved the condensation of barbituric acid with an indanone derivative, followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of 2b was found to have a minimum-energy conformation very similar to that of 1a when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a in vertebrate DHFR. Theoretically such a derivative might have increased specificity and activity against the bacterial enzyme. Molecular modeling experiments suggested that the actual decreased activity was due to crowding in the enzyme, caused by the extra atoms needed to restrict the conformation.

  DOI：

  10.1021/jm00106a011
• 作为产物：
  描述：

  5,6-二甲氧基茚酮 在 哌啶 、 sodium tetrahydroborate 、 氨 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 110.0h， 生成 6-chloro-2,4-diamino-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogs of trimethoprim

  摘要：

  A conformationally restricted analogue of trimethoprim (1a) has been prepared by connecting the ortho position of the benzene ring to the methylene linkage with two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry involved the condensation of barbituric acid with an indanone derivative, followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of 2b was found to have a minimum-energy conformation very similar to that of 1a when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a in vertebrate DHFR. Theoretically such a derivative might have increased specificity and activity against the bacterial enzyme. Molecular modeling experiments suggested that the actual decreased activity was due to crowding in the enzyme, caused by the extra atoms needed to restrict the conformation.

  DOI：

  10.1021/jm00106a011

文献信息

• CHAN, JOSEPH H.;ROTH, BARBARA, J. MED. CHEM., 34,(1991) N, C. 350-355
  作者：CHAN, JOSEPH H.、ROTH, BARBARA

  DOI：——

  日期：——