2-甲基-3-苯基-4-喹啉醇 | 5350-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2-甲基-3-苯基-4-喹啉醇
• 英文名称: 2-methyl-3-phenylquinolin-4-ol
• 英文别名: 2-methyl-3-phenyl-1H-quinolin-4-one
• CAS: 5350-61-8
• 化学式: C₁₆H₁₃NO
• 分子量: 235.285
• InChiKey: OFYQHVQAZBGWIQ-UHFFFAOYSA-N

物化性质

• 熔点：
  302-304 °C (decomp)
• 沸点：
  373.0±37.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-甲基-3-苯基-4-喹啉醇 在 盐酸 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 [4-(3,4-dimethyl-piperazin-1-yl)-phenyl]-(2-methyl-3-phenyl-quinolin-4-yl)-amine
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x
• 作为产物：
  描述：

  2-苯基乙酰乙酸乙酯 在 对甲苯磺酸 作用下， 以 二苯醚 、 甲苯 为溶剂， 反应 1.0h， 生成 2-甲基-3-苯基-4-喹啉醇
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x

文献信息

• The novel reaction of ketones with o-oxazoline-substituted anilines
  作者：Fen-Tair Luo、Vija K. Ravi、Cuihua Xue

  DOI：10.1016/j.tet.2006.07.057

  日期：2006.10

  A variety of ketones react with o-oxazoline-substituted anilines in the presence of catalytic amount of p-toluenesulfonic acid in dry n-butanol to form 4-amino-substituted quinolines or 4-quinolones in fair to good yields.

  在干燥的正丁醇中催化量的对甲苯磺酸存在下，各种酮类与邻恶唑啉取代的苯胺反应，以相当高的收率形成4-氨基取代的喹啉或4-喹诺酮。
• Transition-Metal-Free C-3 Arylation of Quinoline-4-ones with Arylhydrazines
  作者：Makthala Ravi、Parul Chauhan、Ruchir Kant、Sanjeev K. Shukla、Prem. P. Yadav

  DOI：10.1021/acs.joc.5b00739

  日期：2015.5.15

  A transition-metal-free C-3-arylation of quinolin-4-ones in the presence of base has been achieved by using arylhydrazines as aryl radical source and air as oxidant. The reaction proceeds smoothly at room temperature and does not require any prefunctionalization and N-protection of quinoline-4-ones. The utility of this methodology is further demonstrated in synthesis of quinoline–quinolone hybrid as

  通过使用芳基肼作为芳基自由基源和空气作为氧化剂，可以在碱存在下实现喹啉-4-酮的无过渡金属C-3-芳基化。该反应在室温下平稳进行，不需要任何预官能化和喹啉-4-酮的N-保护。该方法的实用性在喹啉-喹诺酮杂化物以及6-芳基-苯并呋喃[3,2- c ]喹啉支架的合成中得到了进一步证明。
• MICROWAVE IRRADIATION PROMOTED REACTIONS OF ANTHRANILIC ACID WITH KETONES. PREPARATION OF SUBSTITUTED ACRIDINONES AND QUINOLINONES
  作者：Mohammad S. Khajavi、Ali A. Mohammadi、S. S. Sadat Hosseini

  DOI：10.1081/scc-100107014

  日期：2001.1

  An efficient synthesis of some new derivatives of acridinones and quinolinones by the condensation of anthranilic acid with ketones under microwave irradiation in unsealed vessels is described.

  描述了在未密封容器中在微波辐射下通过邻氨基苯甲酸与酮缩合有效合成一些新的吖啶酮和喹啉酮衍生物。
• Certain 4-Hydroxyquinolines from Aniline and β-Ketonitriles. Cyclizations of Nitriles through Amides by Means of Polyphosphoric Acid
  作者：Charles R. Hauser、James G. Murray

  DOI：10.1021/ja01615a055

  日期：1955.5
• Endochin Optimization: Structure−Activity and Structure−Property Relationship Studies of 3-Substituted 2-Methyl-4(1<i>H</i>)-quinolones with Antimalarial Activity
  作者：R. Matthew Cross、Andrii Monastyrskyi、Tina S. Mutka、Jeremy N. Burrows、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm1007903

  日期：2010.10.14

  Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of mullidrug resistant W2 and TM90-C2B isolates of Plasmodium folciparum. Follow-up structure activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.