8-methyl-2-<4-(methylthio)phenyl>quinoline-4-carboxylic acid | 117874-51-8

• 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
• 英文名称: 8-methyl-2-<4-(methylthio)phenyl>quinoline-4-carboxylic acid
• 英文别名: 8-methyl-2-(4-(methylthio)phenyl)quinoline-4-carboxylic acid；8-Methyl-2-(4-methylsulfanylphenyl)quinoline-4-carboxylic acid
• CAS: 117874-51-8
• 化学式: C₁₈H₁₅NO₂S
• 分子量: 309.389
• InChiKey: WIFNPQAGNHAMDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-methyl-2-<4-(methylthio)phenyl>quinoline-4-carboxylic acid 在 chromium(VI) oxide 、 盐酸 、 硫酸 、 铜 、 间氯过氧苯甲酸 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 8.58h， 生成 2-(4-Methanesulfonyl-phenyl)-quinoline-8-carboxylic acid (2-dimethylamino-ethyl)-amide; hydrochloride
  参考文献：
  名称：

  Potential antitumor agents. 57. 2-Phenylquinoline-8-carboxamides as minimal DNA-intercalating antitumor agents with in vivo solid tumor activity

  摘要：

  A series of phenyl-substituted derivatives of the "minimal" DNA-intercalating agent N-[2-(dimethylamino)-ethyl]-2-phenylquinoline-8-carboxamide (1) have been synthesized and evaluated for in vivo antitumor activity, in a continuing search for active compounds of this class with the lowest possible DNA association constants. Substitution on the 2'-position of the phenyl ring gave compounds of lower DNA binding ability that did not intercalate DNA, indicating that it is necessary for the phenyl ring to be essentially coplanar with the quinoline for intercalative binding. An extensive series of 4'-substituted derivatives was evaluated, but there was no overall relationship between biological activity and substituent lipophilic or electronic properties. However, several compounds showed good solid tumor activity, with the 4'-aza derivative 18 being clearly superior to the parent compound, effecting about 50% cures in both leukemia and solid tumor models.

  DOI：

  10.1021/jm00122a018
• 作为产物：
  描述：

  7-甲基靛红 、 4-甲硫基苯乙酮 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 以68%的产率得到8-methyl-2-<4-(methylthio)phenyl>quinoline-4-carboxylic acid
  参考文献：
  名称：

  Potential antitumor agents. 57. 2-Phenylquinoline-8-carboxamides as minimal DNA-intercalating antitumor agents with in vivo solid tumor activity

  摘要：

  A series of phenyl-substituted derivatives of the "minimal" DNA-intercalating agent N-[2-(dimethylamino)-ethyl]-2-phenylquinoline-8-carboxamide (1) have been synthesized and evaluated for in vivo antitumor activity, in a continuing search for active compounds of this class with the lowest possible DNA association constants. Substitution on the 2'-position of the phenyl ring gave compounds of lower DNA binding ability that did not intercalate DNA, indicating that it is necessary for the phenyl ring to be essentially coplanar with the quinoline for intercalative binding. An extensive series of 4'-substituted derivatives was evaluated, but there was no overall relationship between biological activity and substituent lipophilic or electronic properties. However, several compounds showed good solid tumor activity, with the 4'-aza derivative 18 being clearly superior to the parent compound, effecting about 50% cures in both leukemia and solid tumor models.

  DOI：

  10.1021/jm00122a018

文献信息

• Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclooxygenase-2 inhibitors
  作者：Afshin Zarghi、Razieh Ghodsi、Ebrahim Azizi、Bahram Daraie、Mehdi Hedayati、Orkideh G. Dadrass

  DOI：10.1016/j.bmc.2009.05.084

  日期：2009.7

  A group of 4-carboxyl quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 structure–activity relationships were determined by varying the substituents on the C-7 and C-8 quinoline ring. Among the 4-carboxyl quinolines, 7,8,9,10-tetrahydro-2-(4-(methyl sulf

  设计并合成了一组在C-2苯环对位具有甲基磺酰基COX-2药效基团的4-羧基喹啉衍生物，作为选择性COX-2抑制剂。通过改变C-7和C-8喹啉环上的取代基来确定体外COX-1 / COX-2的构效关系。在4-羧基喹啉中，将7,8,9,10-四氢-2-（4-（甲基磺酰基）苯基）苯并[ h ]喹啉-4-羧酸（9e）鉴定为有效且高选择性的COX- 2种抑制剂（COX-2 IC 50  = 0.043μM;选择性指数> 513）比参考药物塞来昔布（COX-2 IC 50  = 0.060μM; SI = 405）更有效。分子建模研究，其中9e在COX-2的结合位点对接表明，C-2苯环上的p -MeSO 2取代基位于COX-2二级口袋（Arg513，Phe518和Val523）附近，并且羧基可以相互作用与Arg120。获得的结构活性数据表明，C-7和C-8喹啉环上亲脂性取代基的存在对COX-2抑制活性很重要。
• Potential antitumor agents. 57. 2-Phenylquinoline-8-carboxamides as minimal DNA-intercalating antitumor agents with in vivo solid tumor activity
  作者：Graham J. Atwell、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00122a018

  日期：1989.2

  A series of phenyl-substituted derivatives of the "minimal" DNA-intercalating agent N-[2-(dimethylamino)-ethyl]-2-phenylquinoline-8-carboxamide (1) have been synthesized and evaluated for in vivo antitumor activity, in a continuing search for active compounds of this class with the lowest possible DNA association constants. Substitution on the 2'-position of the phenyl ring gave compounds of lower DNA binding ability that did not intercalate DNA, indicating that it is necessary for the phenyl ring to be essentially coplanar with the quinoline for intercalative binding. An extensive series of 4'-substituted derivatives was evaluated, but there was no overall relationship between biological activity and substituent lipophilic or electronic properties. However, several compounds showed good solid tumor activity, with the 4'-aza derivative 18 being clearly superior to the parent compound, effecting about 50% cures in both leukemia and solid tumor models.