6-ethyl-1-(4-chloro-phenyl)-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 6-ethyl-1-(4-chloro-phenyl)-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride
• 英文别名: 6-Aethyl-1-(4-chlor-phenyl)-1,6-dihydro-[1,3,5]triazin-2,4-diyldiamin; Hydrochlorid；1-(4-chlorophenyl)-2-ethyl-2H-1,3,5-triazine-4,6-diamine;hydrochloride
• 化学式: C₁₁H₁₄ClN₅*ClH
• 分子量: 288.18
• InChiKey: XISFMGJYCDQEMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.95
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80
• 氢给体数：
  3
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-ethyl-1-(4-chloro-phenyl)-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride 在 sodium hydroxide 作用下， 生成 6-ethyl-N²-(4-chloro-phenyl)-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine
  参考文献：
  名称：

  Chemical and Biological Studies on 1,2-Dihydro-s-triazines. III. Two-Component Synthesis^1,2

  摘要：

  DOI：

  10.1021/jo01107a002
• 作为产物：
  描述：

  对氯苯胺 、 丙醛 、 二聚氰胺 在 盐酸 作用下， 以92%的产率得到6-ethyl-1-(4-chloro-phenyl)-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride
  参考文献：
  名称：

  Development of a Lead Inhibitor for the A16V+S108T Mutant of Dihydrofolate Reductase from the Cycloguanil-Resistant Strain (T9/94) of Plasmodium falciparum^†

  摘要：

  The Ala16Val+Ser108Thr (A16V+S108T) mutant of the Plasmodium falciparum dihydrofolate reductase (DHFR) is a key mutant responsible for cycloguanil-resistant malaria due to steric interaction between Val-16 and one of the C-2 methyl groups of cycloguanil. 4,6-Diamino-1,2-dihydrotriazines have been prepared, in which both methyl groups of cycloguanil are replaced by H or by H and an alkyl or phenyl group, and their inhibition constants against wild-type and mutant DHFR determined. The S108T mutation is considered to decrease cycloguanil binding further through the effect on the orientation of the p-chlorophenyl group. By moving the p-chloro-substituent to the m-position in the chlorophenyl group, the activity against the A16V+S108T mutant enzyme is improved, and this effect is reinforced by the p-chloro substituent in the 3,4-dichlorophenyl group. A lead compound has been found with inhibitory activity similar to that of cycloguanil against the wild-type DHFR and about 120-fold more effective than cycloguanil against the A16V+S108T mutant enzyme. The activity of this compound against P. falciparum clone (T9/94 RC17) which harbors the A16V+S108T DHFR is about 85-fold greater than cycloguanil.

  DOI：

  10.1021/jm0009181

文献信息

• Chemical and Biological Studies on 1,2-Dihydro-s-triazines. III. Two-Component Synthesis^1,2
  作者：EDWARD J. MODEST、PHILIP LEVINE

  DOI：10.1021/jo01107a002

  日期：1956.1
• Development of a Lead Inhibitor for the A16V+S108T Mutant of Dihydrofolate Reductase from the Cycloguanil-Resistant Strain (T9/94) of <i>Plasmodium falciparum</i>^†
  作者：Yongyuth Yuthavong、Tirayut Vilaivan、Netnapa Chareonsethakul、Sumalee Kamchonwongpaisan、Worachart Sirawaraporn、Rachel Quarrell、Gordon Lowe

  DOI：10.1021/jm0009181

  日期：2000.7.1

  The Ala16Val+Ser108Thr (A16V+S108T) mutant of the Plasmodium falciparum dihydrofolate reductase (DHFR) is a key mutant responsible for cycloguanil-resistant malaria due to steric interaction between Val-16 and one of the C-2 methyl groups of cycloguanil. 4,6-Diamino-1,2-dihydrotriazines have been prepared, in which both methyl groups of cycloguanil are replaced by H or by H and an alkyl or phenyl group, and their inhibition constants against wild-type and mutant DHFR determined. The S108T mutation is considered to decrease cycloguanil binding further through the effect on the orientation of the p-chlorophenyl group. By moving the p-chloro-substituent to the m-position in the chlorophenyl group, the activity against the A16V+S108T mutant enzyme is improved, and this effect is reinforced by the p-chloro substituent in the 3,4-dichlorophenyl group. A lead compound has been found with inhibitory activity similar to that of cycloguanil against the wild-type DHFR and about 120-fold more effective than cycloguanil against the A16V+S108T mutant enzyme. The activity of this compound against P. falciparum clone (T9/94 RC17) which harbors the A16V+S108T DHFR is about 85-fold greater than cycloguanil.