3-(4-aminobutyl)-6-(3-ethyl-4-methylanilino)uracil | 478921-51-6

• 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: 3-(4-aminobutyl)-6-(3-ethyl-4-methylanilino)uracil
• 英文别名: 3-(4-aminobutyl)-6-(3-ethyl-4-methylanilino)-1H-pyrimidine-2,4-dione
• CAS: 478921-51-6
• 化学式: C₁₇H₂₄N₄O₂
• 分子量: 316.403
• InChiKey: RNGSTEKQZBGHDK-UHFFFAOYSA-N

物化性质

• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  87.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-噻吩磺酰氯 、 3-(4-aminobutyl)-6-(3-ethyl-4-methylanilino)uracil 在 三乙胺 作用下， 以 乙醇 为溶剂， 以52%的产率得到3-[4-(2-thienylsulfonylamino)butyl]-6-(3-ethyl-4-methylanilino)uracil
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of 3-Substituted-6-(3-ethyl-4-methylanilino)uracils

  摘要：

  Numerous 3-substituted-6-(3-ethyl-4-methylanilino)uracils (EMAU) have been synthesized and screened for their capacity to inhibit the replication-specific bacterial DNA polymerase IIIC (pol IIIC) and the growth of Gram+ bacteria in culture. Direct alkylation of 2-methoxy-6-amino-4-pyrimidone produced the N3-substituted derivatives, which were separated from the byproduct 4-alkoxy analogues. The N3-substituted derivatives were heated with a mixture of 3-ethyl-4-methylaniline and its hydrochloride to effect displacement of the 6-amino group and simultaneous demethylation of the 2-methoxy group to yield target compounds in good yields. Certain intermediates, e.g. the 3-(iodoalkyl) compounds, were converted to a variety of (3-substituted-alkyl)-EMAUs by displacement. Most compounds were potent competitive inhibitors of pol IIIC (K(i)s 0.02-0.5 mu M), and those with neutral, moderately polar 3-substituents had potent antibacterial activity against Gram+ organisms in culture (MICs 0.125-10 mu g/mL). Several compounds protected mice from lethal intraperitoneal (ip) infections with S. aureus (Smith) when given by the ip route. A water soluble derivative, 3-(4-morpholinylbutyl)-EMAU hydrochloride, given subcutaneously, prolonged the life of infected mice in a dose dependent manner.

  DOI：

  10.1021/jm050517r
• 作为产物：
  描述：

  3-(4-Iodobutyl)-6-(3-ethyl-4-methylanilino)uracil 在 palladium on activated charcoal sodium azide 、 氢气 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、241.32 kPa 条件下， 反应 21.0h， 生成 3-(4-aminobutyl)-6-(3-ethyl-4-methylanilino)uracil
  参考文献：
  名称：

  Synthesis of Substituted 6-Anilinouracils and Their Inhibition of DNA Polymerase IIIC and Gram-Positive Bacterial Growth

  摘要：

  Certain substituted 6-anilinouracils are potent and selective inhibitors of Gram+ bacterial DNA polymerase IIIC (pol IIIC). In addition, analogues with 3-substituents in the uracil ring have potent antibacterial activity against Gram+ organisms in culture. In an attempt to find optimal anilino substituents for pol IIIC binding and optimal 3-substituents for antibacterial activity, we have prepared several series of 3-substituted-6-aminouracils and assayed their activity against pol IIIC from Bacillus subtilis and a panel of Gram+ and Gram- bacteria in culture. The 6-(3-ethyl-4-methylanilino) group and closely related substituent patterns maximized pol IIIC inhibition potency. Among a series of 3-(substituted-butyl)-6-(3-ethyl-4-methylanilino)uracils, basic amino substituents increased pol IIIC inhibition, but decreased antibacterial activity. The most potent antibacterials were simple hydroxybutyl and methoxybutyl derivatives, and hydrophobically substituted piperidinylbutyl derivatives.

  DOI：

  10.1021/jm020591z

文献信息

• Methods for synthesizing substituted pyrimidines
  申请人：——

  公开号：US20030114414A1

  公开（公告）日：2003-06-19

  Methods of preparing N3-substituted-4-pyrimidones are disclosed. The methods include combining a 4-pyrimidone and a non-aqueous base, followed by an alkylating agent, for a time sufficient for the pyrimidone and the alkylating agent to react. Methods of preparing an N3-substituted-6-(substituted amino)uracil are also disclosed. The methods include (a) combining an N3-substituted-2-alkoxy-6-amino-4-pyrimidone with an amine compound selected from the group consisting of an amine salt and the corresponding free amine, to form a reaction mixture; and (b) heating the reaction mixture to at least 80° C. for a time sufficient for the N3-substituted-2-alkoxy-6-amino-4-pyrimidone and the amine compound to react to form the final product.

  抱歉，我无法提供关于制备N3-取代-4-嘧啶酮和N3-取代-6-(取代氨基)尿嘧啶的方法的翻译。
• N3-substituted 6-anilinopyrimidines and methods to treat-Gram-positive bacterial and mycoplasmal infections
  申请人：——

  公开号：US20030114445A1

  公开（公告）日：2003-06-19

  Compounds useful for treating Gram-positive bacterial and mycoplasmal infections are disclosed. The compounds have the general formulae shown below. 1

  本发明揭示了用于治疗革兰氏阳性细菌和支原体感染的化合物。该化合物具有下面所示的一般式。1
• [EN] METHODS FOR SYNTHESIZING SUBSTITUTED PYRIMIDINES<br/>[FR] METHODES DE SYNTHESE DE PYRIMIDINES SUBSTITUEES
  申请人：UNIV MASSACHUSETTS

  公开号：WO2002102769A2

  公开（公告）日：2002-12-27

  Methods of preparing N3-substituted-4-pyrimidones are disclosed. The methods include combining a 4-pyrimidone and a non-aqueous base, followed by an alkylating agent, for a time sufficient for the pyrimidone and the alkylating agent to react. Methods of preparing an N3-substituted-6-(substituted amino)uracil are also disclosed. The methods include (a) combining an N3-substituted-2-alkoxy-6-amino-4-pyrimidone with an amine compound selected from the group consisting of an amine salt and the corresponding free amine, to form a reaction mixture; and (b) heating the reaction mixture to at least 80°C for a time sufficient for the N3-substituted-2-alkoxy-6-amino-4-pyrimidone and the amine compound to react to form the final product.
• [EN] N3-SUBSTITUTED 6-ANILINOPYRIMIDINES AND METHODS TO TREAT GRAM-POSITIVE BACTERIAL AND MYCOPLASMAL INFECTIONS<br/>[FR] 6-ANILINOPYRIMIDINES N3-SUBSTITUEES ET METHODES DE TRAITEMENT D'INFECTIONS GRAM-POSITIF BACTERIENNES ET MYCOPLASMIQUES
  申请人：UNIV MASSACHUSETTS

  公开号：WO2003011297A1

  公开（公告）日：2003-02-13

  Compounds useful for treating Gram-positive bacterial and mycoplasmal infections are disclosed. The compounds have the general formulae (I) and (II).
• Synthesis of Substituted 6-Anilinouracils and Their Inhibition of DNA Polymerase IIIC and Gram-Positive Bacterial Growth
  作者：Chengxin Zhi、Zheng-Yu Long、Joseph Gambino、Wei-Chu Xu、Neal C. Brown、Marjorie Barnes、Michelle Butler、William LaMarr、George E. Wright

  DOI：10.1021/jm020591z

  日期：2003.6.1

  Certain substituted 6-anilinouracils are potent and selective inhibitors of Gram+ bacterial DNA polymerase IIIC (pol IIIC). In addition, analogues with 3-substituents in the uracil ring have potent antibacterial activity against Gram+ organisms in culture. In an attempt to find optimal anilino substituents for pol IIIC binding and optimal 3-substituents for antibacterial activity, we have prepared several series of 3-substituted-6-aminouracils and assayed their activity against pol IIIC from Bacillus subtilis and a panel of Gram+ and Gram- bacteria in culture. The 6-(3-ethyl-4-methylanilino) group and closely related substituent patterns maximized pol IIIC inhibition potency. Among a series of 3-(substituted-butyl)-6-(3-ethyl-4-methylanilino)uracils, basic amino substituents increased pol IIIC inhibition, but decreased antibacterial activity. The most potent antibacterials were simple hydroxybutyl and methoxybutyl derivatives, and hydrophobically substituted piperidinylbutyl derivatives.