1-(3,4-dichloro-phenyl)-6-phenyl-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride | 109495-67-2

• 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: 1-(3,4-dichloro-phenyl)-6-phenyl-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride
• 英文别名: 1-(3,4-Dichlor-phenyl)-6-phenyl-1,6-dihydro-[1,3,5]triazin-2,4-diyldiamin; Hydrochlorid；1-(3',4'-Dichlorophenyl)-2-phenyl-4,6-diamino-1,2-dihydro-1,3,5-triazine hydrochloride；1-(3,4-dichlorophenyl)-2-phenyl-2H-1,3,5-triazine-4,6-diamine;hydrochloride
• CAS: 109495-67-2
• 化学式: C₁₅H₁₃Cl₂N₅*ClH
• 分子量: 370.669
• InChiKey: ITQZPOBHDFLUJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.43
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  79.4
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  苯甲醛 、 二聚氰胺 、 3,4-二氯苯胺 在 盐酸 作用下， 以63%的产率得到1-(3,4-dichloro-phenyl)-6-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

• Dihydrofolate reductase inhibitors
  申请人：——

  公开号：US20030203908A1

  公开（公告）日：2003-10-30

  A compound of formula (I) or (II), wherein X is hydrogen, halogen, alkyl, aralkyl,aryloxy, arylalkoxy or alkoxy, Y is hydrogen, halogen, alkyl, aralkyl, aryloxy, arylalkoxy or alkoxy, or formula (a) wherein A and B are different and one of A and B is CH 2 and the other is O, NH, or S or A and B are both CH 2 or CH═, and R a , R b , and R c are the same or different and are hydrogen, halogen, alkyl, alkoxy, aryloxy, aralkyl or arylalkoxy. R 1 is hydrogen, and R 2 is hydrogen, C 1 -C 6 alkyl or aryl which is unsubstituted or substituted by halogen, cyano, hydroxy, C 1 -C 6 alkyl, which is unsubstituted or substituted by halogen, cyano, hydroxy, C 1 -C 6 alkoxy, aralkyl, aryloxy or aryl, C 1 -C 6 alkoxy, aralkyl, arylalkoxy, aryloxy or aryl, which is unsubstituted or substituted by halogen, cyano, hydroxy, C 1 -C 6 alkyl or C 1 -C 6 alkoxy; and pharmaceutically acceptable salts thereof; with the proviso that when R 2 is phenyl and Y is hydrogen, X is not chlorine. 1

  化合物的化学式(I)或(II)，其中X为氢、卤素、烷基、芳基烷基、芳氧基、芳基烷氧基或烷氧基，Y为氢、卤素、烷基、芳基烷基、芳氧基、芳基烷氧基或烷氧基，或者化学式(a)中A和B不同，A和B中之一为CH2，另一个为O、NH或S，或者A和B都为 或CH═，而Ra、Rb和Rc相同或不同，分别为氢、卤素、烷基、烷氧基、芳氧基、芳基烷基或芳基烷氧基。R1为氢，R2为氢、C1-C6烷基或芳基，未被卤素、氰基、羟基、C1-C6烷基（未被卤素、氰基、羟基、C1-C6烷氧基、芳基烷基、芳氧基或芳基取代）取代或取代的烷基、芳基烷基、芳基烷氧基、芳氧基或芳基，未被卤素、氰基、羟基、C1-C6烷基或C1-C6烷氧基取代或取代的烷基、芳基烷基、芳基烷氧基、芳氧基或芳基；以及其药学上可接受的盐；但当R2为苯基且Y为氢时，X不为氯。
• [EN] DIHYDROFOLATE REDUCTASE INHIBITORS<br/>[FR] INHIBITEURS DE LA DIHYDROFOLATE REDUCTASE
  申请人：ISIS INNOVATION

  公开号：WO2001053276A1

  公开（公告）日：2001-07-26

  A compound of formula (I) or (II), wherein X is hydrogen, halogen, alkyl, aralkyl,aryloxy, arylalkoxy or alkoxy, Y is hydrogen, halogen, alkyl, aralkyl, aryloxy, arylalkoxy or alkoxy, or formula (a) wherein A and B are different and one of A and B is CH2 and the other is O, NH, or S or A and B are both CH2 or CH=, and R?a, Rb, and Rc¿ are the same or different and are hydrogen, halogen, alkyl, alkoxy, aryloxy, aralkyl or arylalkoxy. R1 is hydrogen, and R2 is hydrogen, C¿1?-C6 alkyl or aryl which is unsubstituted or substituted by halogen, cyano, hydroxy, C1-C6 alkyl, which is unsubstituted or substituted by halogen, cyano, hydroxy, C1-C6 alkoxy, aralkyl, aryloxy or aryl, C1-C6 alkoxy, aralkyl, arylalkoxy, aryloxy or aryl, which is unsubstituted or substituted by halogen, cyano, hydroxy, C1-C6 alkyl or C1-C6 alkoxy; and pharmaceutically acceptable salts thereof; with the proviso that when R?2¿ is phenyl and Y is hydrogen, X is not chlorine.