1,6-diphenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride | 97376-33-5

• 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: 1,6-diphenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride
• 英文别名: 4,6-diamino-1,2-dihydro-1,2-diphenyl-1,3,5-triazine hydrochloride；1,6-diphenyl-1,6-dihydro-[1,3,5]triazine-2,4-diyldiamine; hydrochloride；1,6-Diphenyl-1,6-dihydro-[1,3,5]triazin-2,4-diyldiamin; Hydrochlorid；1,2-diphenyl-2H-1,3,5-triazine-4,6-diamine;hydrochloride
• CAS: 97376-33-5
• 化学式: C₁₅H₁₅N₅*ClH
• 分子量: 301.779
• InChiKey: IZQDNVCXOYHSOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.26
• 重原子数：
  21
• 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：
  80
• 氢给体数：
  3
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,6-diphenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以1.4 g的产率得到N²,6-diphenyl-5,6-dihydro-1,3,5-triazine-2,4-diamine
  参考文献：
  名称：

  一锅法合成 N2,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines 并系统评估它们在晶体中承载乙醇的能力†

  摘要：

  使用 1,6-二芳基的三组分合成开发了一种方便的一锅法制备N 2 ,6-二芳基-5,6-二氢-1,3,5-三嗪-2,4-二胺-1,6-dihydro-1,3,5-triazine-2,4-diamines，然后将它们的 Dimroth 重排为所需的产物。制备的化合物以乙醇包合物(1:1)的形式从乙醇中结晶出来。几种产品的 X 射线晶体学证实采用了 5,6-二氢互变异构体。对选定化合物的热分析和粉末 X 射线衍射实验表明，晶体的热去溶剂化是不可逆的。

  DOI：

  10.1039/c9ra08795h
• 作为产物：
  描述：

  苯胺 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 4.17h， 生成 1,6-diphenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride
  参考文献：
  名称：

  Structural Insights into the Development of Cycloguanil Derivatives asTrypanosoma bruceiPteridine-Reductase-1 Inhibitors

  摘要：

  Cycloguanil is a known dihydrofolate-reductase (DHFR) inhibitor, but there is no evidence of its activity on pteridine reductase (PTR), the main metabolic bypass to DHFR inhibition in trypanosomatid parasites. Here, we provide experimental evidence of cycloguanil as an inhibitor of Trypanosoma brucei PTR1 (TbPTR1). A small library of cycloguanil derivatives was developed, resulting in 1 and 2a having IC50 values of 692 and 186 nM, respectively, toward TbPTR1. Structural analysis revealed that the increased potency of 1 and 2a is due to the combined contributions of hydrophobic interactions, H-bonds, and halogen bonds. Moreover, in vitro cell-growth-inhibition tests indicated that 2a is also effective on T. brucei. The simultaneous inhibition of DHFR and PTR1 activity in T. brucei is a promising new strategy for the treatment of human African trypanosomiasis. For this purpose, 1,6-dihydrotriazines represent new molecular tools to develop potent dual PTR and DHFR inhibitors.

  DOI：

  10.1021/acsinfecdis.8b00358

文献信息

• New One-Pot Synthesis of 1,3,5-Triazines: Three-Component Condensation, Dimroth Rearrangement, and Dehydrogenative Aromatization
  作者：Ahmad Junaid、Felicia Phei Lin Lim、Edward R. T. Tiekink、Anton V. Dolzhenko

  DOI：10.1021/acscombsci.9b00079

  日期：2019.7.8

  A new, effective one-pot synthesis of the 6,N2-diaryl-1,3,5-triazine-2,4-diamines under microwave irradiation was developed. The method involved an initial three-component condensation of cyanoguanidine, aromatic aldehydes, and arylamines in the presence of hydrochloric acid. Without isolation, the resulting 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines were treated with a base to initiate Dimroth

  开发了一种在微波辐射下有效合成一锅6，N 2-二芳基-1,3,5-三嗪-2,4-二胺的新方法。该方法涉及在盐酸存在下氰基胍，芳族醛和芳基胺的初始三组分缩合。不经分离，将所得的1,6-二芳基-1,6-二氢-1,3,5-三嗪-2,4-二胺用碱处理以引发Dimroth重排和自发脱氢芳构化，得到所需化合物。发现所开发的方法在范围上足够通用，可以耐受各种芳族醛和胺。通过在第一步中使用它们的组合，成功制备了110种化合物的代表性文库，并筛选了其抗癌特性。
• Synthesis of Solution-Phase Combinatorial Library of 4,6-Diamino-1,2-dihydro-1,3,5-triazine and Identification of New Leads Against A16V+S108T Mutant Dihydrofolate Reductase of Plasmodium falciparum
  作者：Tirayut Vilaivan、Neungruthai Saesaengseerung、Deanpen Jarprung、Sumalee Kamchonwongpaisan、Worachart Sirawaraporn、Yongyuth Yuthavong

  DOI：10.1016/s0968-0896(02)00344-9

  日期：2003.1

  An efficient method to synthesize solution-phase combinatorial library of 1-aryl-4,6-diamino-1,2-dihydro-1,3,5-triazine was developed. The strategy involved an acid-catalyzed cyclocondensation between arylbiguanide hydrochlorides and carbonyl compounds in the presence of triethyl orthoacetate as water scavenger. A 96-membered combinatorial library was constructed from 6 aryl biguanides and 16 carbonyl compounds. Screening of the library by iterative deconvolution method revealed two candidate leads which are equally active against wild-type Plasmodium falciparum dihydrofolate reductase, but are about 100-fold more effective against the A16V + S108T mutant enzyme as compared to cycloguanil. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 1-Aryl-4,6-diamino-1,2-dihydrotriazine as antimalarial agent: a new synthetic route
  作者：M. Kidwai、P. Mothsra、R. Mohan、S. Biswas

  DOI：10.1016/j.bmcl.2004.12.049

  日期：2005.2

  Some novel derivatives of 1-aryl-4,6-diamino-1,2-dihydrotriazines have been synthesized using neat technology under microwaves. These were tested in vitro against both sensitive and resistant Plasmodium falciparum strains for antimalarial activity. (C) 2004 Elsevier Ltd. All rights reserved.
• A one-pot synthesis of <i>N</i>²,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines and systematic evaluation of their ability to host ethanol in crystals
  作者：Ahmad Junaid、Yee Seng Tan、Edward R. T. Tiekink、Anton V. Dolzhenko

  DOI：10.1039/c9ra08795h

  日期：——

  A convenient one-pot method for the preparation of N2,6-diaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines was developed using a three-component synthesis of 1,6-diaryl-1,6-dihydro-1,3,5-triazine-2,4-diamines followed by their Dimroth rearrangement to the desired products. The prepared compounds crystallized from ethanol as ethanol clathrates (1 : 1). X-ray crystallography on several products confirmed

  使用 1,6-二芳基的三组分合成开发了一种方便的一锅法制备N 2 ,6-二芳基-5,6-二氢-1,3,5-三嗪-2,4-二胺-1,6-dihydro-1,3,5-triazine-2,4-diamines，然后将它们的 Dimroth 重排为所需的产物。制备的化合物以乙醇包合物(1:1)的形式从乙醇中结晶出来。几种产品的 X 射线晶体学证实采用了 5,6-二氢互变异构体。对选定化合物的热分析和粉末 X 射线衍射实验表明，晶体的热去溶剂化是不可逆的。
• Structural Insights into the Development of Cycloguanil Derivatives as<i>Trypanosoma brucei</i>Pteridine-Reductase-1 Inhibitors
  作者：Giacomo Landi、Pasquale Linciano、Chiara Borsari、Claudia P. Bertolacini、Carolina B. Moraes、Anabela Cordeiro-da-Silva、Sheraz Gul、Gesa Witt、Maria Kuzikov、Maria Paola Costi、Cecilia Pozzi、Stefano Mangani

  DOI：10.1021/acsinfecdis.8b00358

  日期：2019.7.12

  Cycloguanil is a known dihydrofolate-reductase (DHFR) inhibitor, but there is no evidence of its activity on pteridine reductase (PTR), the main metabolic bypass to DHFR inhibition in trypanosomatid parasites. Here, we provide experimental evidence of cycloguanil as an inhibitor of Trypanosoma brucei PTR1 (TbPTR1). A small library of cycloguanil derivatives was developed, resulting in 1 and 2a having IC50 values of 692 and 186 nM, respectively, toward TbPTR1. Structural analysis revealed that the increased potency of 1 and 2a is due to the combined contributions of hydrophobic interactions, H-bonds, and halogen bonds. Moreover, in vitro cell-growth-inhibition tests indicated that 2a is also effective on T. brucei. The simultaneous inhibition of DHFR and PTR1 activity in T. brucei is a promising new strategy for the treatment of human African trypanosomiasis. For this purpose, 1,6-dihydrotriazines represent new molecular tools to develop potent dual PTR and DHFR inhibitors.