HB-EMAU | 292619-96-6

• 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: HB-EMAU
• 英文别名: 3-(4-hydroxybutyl)-6-(3-ethyl-4-methylanilino)uracil；6-(3-ethyl-4-methylanilino)-3-(4-hydroxybutyl)-1H-pyrimidine-2,4-dione
• CAS: 292619-96-6
• 化学式: C₁₇H₂₃N₃O₃
• 分子量: 317.388
• InChiKey: DKZBKKHAGYCGJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  81.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  HB-EMAU 在 碘代三甲硅烷 作用下， 以 氯仿 为溶剂， 生成 3-(4-Iodobutyl)-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：

  1-(4-methoxybutyl)barbituric acid 在 苄基三乙基氯化铵 、 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 3.5h， 生成 HB-EMAU
  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。
• Novel heterocyclic antibacterial compounds
  申请人：——

  公开号：US20030181719A1

  公开（公告）日：2003-09-25

  The invention provides heterocyclic organic compounds that inhibit bacterial DNA polymerase IIIC and type II bacterial topoisomerase. The invention further provides compounds that are useful as intermediates in the synthesis of such heterocyclic organic compounds. Syntheses and uses of such heterocyclic organic molecules are also described.

  该发明提供了抑制细菌DNA聚合酶IIIC和类型II细菌拓扑异构酶的杂环有机化合物。该发明还提供了在合成这种杂环有机化合物中作为中间体有用的化合物。该发明还描述了这种杂环有机分子的合成和用途。
• 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
• SELECTIVE ANTIBACTERIALS FOR CLOSTRIDIUM DIFFICILE INFECTIONS
  申请人：Wright George E.

  公开号：US20120232077A1

  公开（公告）日：2012-09-13

  The invention features compounds of formula (I): The compounds are useful as antibacterial agents, especially again Clostridium difficile -associated diseases.

  这项发明涉及公式（I）的化合物：这些化合物可用作抗菌剂，特别是用于治疗与难辨梭菌相关的疾病。
• [EN] NOVEL HETEROCYCLIC ANTIBACTERIAL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES ANTIBACTERIENS HETEROCYCLIQUES
  申请人：MICROBIOTIX INC

  公开号：WO2002102792A1

  公开（公告）日：2002-12-27

  The invention provides heterocyclic organic compounds that inhibit bacterial DNA polymerase IIIC and type II bacterial topoisomerase. The invention further provides compounds that are useful as intermediates in the synthesis of such heterocyclic organic compounds. Syntheses and uses of such heterocyclic organic molecules are also described.

  本发明提供了一些杂环有机化合物，可抑制细菌DNA聚合酶IIIC和II型细菌拓扑异构酶。本发明还提供了一些化合物，可用作合成此类杂环有机化合物的中间体。本发明还描述了这种杂环有机分子的合成和用途。