2-(4-chlorophenyl)-2,5-cyclohexadiene-1,4-dione 4-oxime | 79287-41-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(4-chlorophenyl)-2,5-cyclohexadiene-1,4-dione 4-oxime
• CAS: 79287-41-5
• 化学式: C₁₂H₈ClNO₂
• 分子量: 233.654
• InChiKey: YVUYIRZLBYYUOV-GXDHUFHOSA-N

物化性质

• 熔点：
  182-184 °C (decomp)
• 沸点：
  418.7±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.66
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(4-chlorophenyl)-2,5-cyclohexadiene-1,4-dione 4-oxime 在 sodium dithionite 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 N-(4'-chloro-6-hydroxy<1,1'-biphenyl>-3-yl)acetamide
  参考文献：
  名称：

  Antimalarial drugs. 60. Synthesis, antimalarial activity, and quantitative structure-activity relationships of tebuquine and a series of related 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl][1,1'-biphenyl]-2-ols and N.omega.-oxides

  摘要：

  A series of 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl] [1,1'-biphenyl]-2-ols and N omega-oxides was prepared from the substituted 1-phenyl-2-propanones proceeding through the 5-nitro[1,1'-biphenyl]-2-ols, the corresponding amino, and acetamido derivatives to the N-[5-[(alkylamino)methyl]-6-hydroxy[1,1'-biphenyl]-3-yl]acetamides and final condensation with 4,7-dichloroquinoline or the N-oxide. In a quantitative structure-activity relationship study first run on 28 and later expanded to 40 substituted phenyl analogues and their N omega-oxides, increasing antimalarial potency vs. Plasmodium berghei in mice was found to be correlated with decreasing size (sigma MR) and electron donation (sigma sigma) of the phenyl ring substituents. A significant correlation with N omega-oxidation could not be demonstrated. Initial high activity against P. berghei infections in mice led to expanded studies that demonstrated in addition excellent activity against resistant strains of parasite, activity in primate models, and pharmacokinetic properties apparently allowing protection against infection for extended periods of time even after oral administration. Such properties encourage the clinical trial of a member of this class in man.

  DOI：

  10.1021/jm00156a009
• 作为产物：
  描述：

  4-chloro-2'-hydroxybiphenyl 在 水 、 溶剂黄146 、 sodium nitrite 作用下， 以26%的产率得到2-(4-chlorophenyl)-2,5-cyclohexadiene-1,4-dione 4-oxime
  参考文献：
  名称：

  Antimalarial drugs. 60. Synthesis, antimalarial activity, and quantitative structure-activity relationships of tebuquine and a series of related 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl][1,1'-biphenyl]-2-ols and N.omega.-oxides

  摘要：

  A series of 5-[(7-chloro-4-quinolinyl)amino]-3-[(alkylamino)methyl] [1,1'-biphenyl]-2-ols and N omega-oxides was prepared from the substituted 1-phenyl-2-propanones proceeding through the 5-nitro[1,1'-biphenyl]-2-ols, the corresponding amino, and acetamido derivatives to the N-[5-[(alkylamino)methyl]-6-hydroxy[1,1'-biphenyl]-3-yl]acetamides and final condensation with 4,7-dichloroquinoline or the N-oxide. In a quantitative structure-activity relationship study first run on 28 and later expanded to 40 substituted phenyl analogues and their N omega-oxides, increasing antimalarial potency vs. Plasmodium berghei in mice was found to be correlated with decreasing size (sigma MR) and electron donation (sigma sigma) of the phenyl ring substituents. A significant correlation with N omega-oxidation could not be demonstrated. Initial high activity against P. berghei infections in mice led to expanded studies that demonstrated in addition excellent activity against resistant strains of parasite, activity in primate models, and pharmacokinetic properties apparently allowing protection against infection for extended periods of time even after oral administration. Such properties encourage the clinical trial of a member of this class in man.

  DOI：

  10.1021/jm00156a009

文献信息

• Substituted-5-((7-chloro-4-quinolinyl)amino)-3-(amino-methyl)-(1,1'-biphenyl)-2-ol compounds; processes for their production; and pharmaceutical compositions containing the compounds
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0027679A2

  公开（公告）日：1981-04-29

  Substituted-5-[(7-chloro-4-quinohny))amino]-3-(aminomethyl)-[(1,1'-biphenyl]-2-ol compounds and salts thereof; and processes for their production are disclosed. In addition, antimalarial pharmaceutical compositions including such compounds and methods of treatment employing the compositions are taught. Also disclosed are intermediates for use in producing the substituted compounds. The substituted compounds are those of the formula:- wherein X is a hydrogen, fluorine, bromine or chlorine atom or a lower alkyl radical; Y is a chlorine, fluorine or bromine atom or a trifluoromethyl, lower alkoxy, cyano, hydroxy, nitro, lower alkylthio, amino, lower alkyl amino, di(lower alkyl) amino, pyrrolidino or piperidino radical; R'and R2, which are the same or different, are each a hydrogen atom or a lower alkyl radical, or R1R2N taken together is a pyrrolidino, piperidino or homopiperidino radical of which the heterocyclic ring is unsubstituted or substituted by from one to four lower alkyl radicals; Z is zero or one.

  公开了取代的-5-[(7-氯-4-喹啉))氨基]-3-(氨基甲基)-[(1,1'-联苯]-2-醇化合物及其盐类；以及生产它们的工艺。此外，还教导了包括此类化合物的抗疟药物组合物和使用该组合物的治疗方法。还公开了用于生产取代化合物的中间体。取代的化合物是那些式如下的化合物 其中 X 是氢、氟、溴或氯原子或低级烷基自由基；Y 是氯、氟或溴原子或三氟甲基、低级烷氧基、氰基、羟基、硝基、低级烷硫基、氨基、低级烷基氨基、二（低级烷基）氨基、吡咯烷基或哌啶基自由基；R'和 R2（相同或不同）各自为氢原子或低级烷基，或 R1R2N 合在一起为吡咯烷基、哌啶基或均哌啶基，其中杂环未被取代或被 1 至 4 个低级烷基取代；Z 为 0 或 1。