2,4-diamino-6-dimethylaminoquinazoline | 141400-10-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,4-diamino-6-dimethylaminoquinazoline
• 英文别名: 6-N,6-N-dimethylquinazoline-2,4,6-triamine
• CAS: 141400-10-4
• 化学式: C₁₀H₁₃N₅
• 分子量: 203.247
• InChiKey: IDRNKSCTPZAYSQ-UHFFFAOYSA-N

物化性质

• 沸点：
  502.0±60.0 °C(Predicted)
• 密度：
  1.332±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-dimethylamino-2-nitrobenzonitrile 在 tin 作用下， 以 盐酸 、 二乙二醇二甲醚 为溶剂， 反应 3.33h， 生成 2,4-diamino-6-dimethylaminoquinazoline
  参考文献：
  名称：

  Antifolate and antibacterial activities of 6-substituted 2,4-diaminoquinazolines

  摘要：

  6-Substituted 2,4-diaminoquinazolines (1) are good inhibitors of dihydrofolate reductase (DHFR) and effective as growth inhibitors of intact bacterial cells in vitro. The most potent compounds in the in vitro tests were, however, ineffective against a systemic murine infection. Quantitative correlations were obtained between DHFR inhibition and the substituent constant molar refractivity (MR) for 3 of the 4 enzymes studied (Escherichia coli, Streptococcus faecalis, and bovine liver DHFR); for the fourth enzyme (Staphylococcus aureus DHFR) the best correlation was obtained with a combination of MR and the lipophilic parameter pi. The recognition that the conformational properties of the 6-substituent may play a vital role in mediating the binding of 1 to DHFR prompted the synthesis of novel analogues specifically designed to test this hypothesis. From these results it was possible to construct a simple schematic model of the binding site occupied by the 6-substituents; a subsequent molecular modelling study agreed with the features of this model.

  DOI：

  10.1016/0223-5234(92)90054-5

文献信息

• Fragment based search for small molecule inhibitors of HIV-1 Tat-TAR
  作者：Mirco Zeiger、Sebastian Stark、Elisabeth Kalden、Bettina Ackermann、Jan Ferner、Ute Scheffer、Fatemeh Shoja-Bazargani、Veysel Erdel、Harald Schwalbe、Michael W. Göbel

  DOI：10.1016/j.bmcl.2014.11.004

  日期：2014.12

  Basic molecular building blocks such as benzene rings, amidines, guanidines, and amino groups have been combined in a systematic way to generate ligand candidates for HIV-1 TAR RNA. Ranking of the resulting compounds was achieved in a fluorimetric Tat-TAR competition assay. Although simple molecules such as phenylguanidine are inactive, few iteration steps led to a set of ligands with IC50 values ranging from 40 to 150 mu M. 1,7-Diaminoisoquinoline 17 and 2,4,6-triaminoquinazoline 22 have been further characterized by NMR titrations with TAR RNA. Compound 22 is bound to TAR at two high affinity sites and shows slow exchange between the free ligand and the RNA complex. These results encourage investigations of dimeric ligands built from two copies of compound 22 or related heterocycles. (C) 2014 Elsevier Ltd. All rights reserved.
• [EN] ANTIFOLATE QUINAZOLINES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：WO1993013079A1

  公开（公告）日：1993-07-08

  (EN) The present invention relates to certain quinazoline compounds capable of inhibiting folate metabolic pathways, to pharmaceutical compositions containing these compounds, and to the use of these compounds to inhibit folate metabolic pathways, including all effects derived from the inhibition of folate metabolic pathways. Effects derived from the inhibition of folate metabolic pathways include the inhibition of the growth and proliferation of the cells of higher organisms and microorganisms, such as bacteria, yeasts and fungi. Such effects may include the inhibition of the enzymes thymidylate synthase or dihydrofolate reductase, or both. A process for preparing the quinazoline antifolate compounds according to the present invention is also disclosed.(FR) On décrit certains composés de quinazoline pouvant inhiber les voies métaboliques des folates, des compositions pharmaceutiques les contenant, et leur utilisation dans l'inhibition des voies métaboliques des folates, notamment tous les effets dérivés de l'inhibition des voies métaboliques des folates. Les effets dérivés de l'inhibition des voies métaboliques des folates sont notamment l'inhibition de la croissance et de la prolifération des cellules des organismes supérieurs et des microorganismes, par exemple les bactéries, les levures et les champignons. Ces effets comprennent éventuellement l'inhibition des enzymes thymidylate-synthase et/ou dihydrofolate-réductase. On a également prévu un procédé de préparation de ces composés anti-folates de quinazoline.
• Antifolate and antibacterial activities of 6-substituted 2,4-diaminoquinazolines
  作者：NV Harris、C Smith、K Bowden

  DOI：10.1016/0223-5234(92)90054-5

  日期：1992.1

  6-Substituted 2,4-diaminoquinazolines (1) are good inhibitors of dihydrofolate reductase (DHFR) and effective as growth inhibitors of intact bacterial cells in vitro. The most potent compounds in the in vitro tests were, however, ineffective against a systemic murine infection. Quantitative correlations were obtained between DHFR inhibition and the substituent constant molar refractivity (MR) for 3 of the 4 enzymes studied (Escherichia coli, Streptococcus faecalis, and bovine liver DHFR); for the fourth enzyme (Staphylococcus aureus DHFR) the best correlation was obtained with a combination of MR and the lipophilic parameter pi. The recognition that the conformational properties of the 6-substituent may play a vital role in mediating the binding of 1 to DHFR prompted the synthesis of novel analogues specifically designed to test this hypothesis. From these results it was possible to construct a simple schematic model of the binding site occupied by the 6-substituents; a subsequent molecular modelling study agreed with the features of this model.