4-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline | 1269183-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline
• 英文别名: 4-(Trifluoromethyl)pyrrolo[1,2-a]quinoxaline
• CAS: 1269183-11-0
• 化学式: C₁₂H₇F₃N₂
• 分子量: 236.196
• InChiKey: GXJLNIBFUWZWJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  17.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-氨基苯基)吡咯 在 三乙胺 、 三氯乙腈 、 三苯基膦 、 三氯氧磷 作用下， 以 吡啶 、 乙腈 为溶剂， 反应 4.0h， 生成 4-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines as new antiplasmodial agents

  摘要：

  Thanks to a preliminary in vitro screening of several CCl3-substituted-nitrogen containing heterocycles belonging to our chemical library, the 2-trichloromethylquinoxaline scaffold appeared to be of potential interest for developing new antiplasmodial agents. Then, combining these experimental results to the antimalarial properties reported for various pyrrolo[1,2-a]quinoxaline derivatives, an original series of fifteen 7-substituted-4-trichoromethylpyrrolo[1,2-a]quinoxalines was synthesized in a 4 to 5 reaction steps pathway. All molecules were evaluated in vitro toward both their antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were identified, displaying IC50 values in the micromolar range and low cytotoxicity values, reaching good selectivity indexes, in comparison with the reference drugs chloroquine and doxycycline. Structure-activity relationship studies showed that the pyrrolo[1,2-a]quinoxaline scaffold can support selective antiplasmodial activity when substituted at position 4 by a CCl3 group. However, substitution at position 7 of the same scaffold is neither beneficial for cytotoxicity nor favourable for the solubility in the biological media.

  DOI：

  10.1016/j.ejmech.2014.06.014

文献信息

• A Radical-Mediated Approach to the Total Synthesis of Fluorinated Marinoquinoline A and Related Tricyclic and Tetracyclic Congeners
  作者：Stephen Hilton、Bhaven Patel

  DOI：10.1055/s-0034-1378614

  日期：——

  A radical-mediated approach to the core structure of fluorinated marinoquinoline A, N-methylated marinoquinoline A and related congeners via the use of Togni’s reagent is described.

  描述了通过使用 Togni 试剂对氟化海洋喹啉 A、N-甲基化海洋喹啉 A 和相关同系物的核心结构进行自由基介导的方法。
• Synthesis of 6-trifluoromethylindolo[1,2-c]quinazolines and related heterocycles using N-(2-iodophenyl)trifluoroacetimidoyl chlorides as starting material via C–H bond functionalization
  作者：Jiangtao Zhu、Haibo Xie、Zixian Chen、Shan Li、Yongming Wu

  DOI：10.1039/c0cc03197f

  日期：——

  A mild, two-step reaction for the synthesis of 6-trifluoromethylindolo[1,2-c]quinazolines from readily available indoles and N-(2-iodophenyl)trifluoroacetimidoyl chlorides via addition-elimination/arylation is described. An array of aza-fused trifluoromethylated heterocycles can be easily assembled via Friedel-Crafts reaction/C-H bond activation by this methodology.

  描述了一种温和的两步反应，该反应通过加成消除/芳基化反应从易得的吲哚和N-（2-碘苯基）三氟乙酰亚胺基氯合成6-三氟甲基吲哚并[1,2-c]喹唑啉。通过该方法，通过Friedel-Crafts反应/ CH键活化，可以容易地组装一系列氮杂稠合的三氟甲基化杂环。
• A Direct Method for Synthesis of Fluorinated Quinazolinones and Quinoxalines Using Fluorinated Acids without Metals or Additives
  作者：Chen Ma、Shichen Li、Xueyan Lv、Jianing Ren、Lei Feng

  DOI：10.1055/a-1824-6352

  日期：2022.9

  ketones, and heterocycles has been studied constantly in recent decades. Herein, a direct method using trifluoroacetic acid as a CF3 source for the synthesis of 2-(trifluoromethyl)quinazolin-4-ones and 4-(trifluoromethyl)pyrrolo/indolo[1,2-a]quinoxalines without any catalysts or additives is reported; a wide range of fluorinated compounds were obtained in 52%–94% yield.

  三氟甲基仅存在于合成化合物中。由于该组独特的生物活性，近几十年来一直在不断研究烷烃、芳烃、烯烃、醛和酮等不饱和化合物以及杂环的三氟甲基化。在此，使用三氟乙酸作为 CF 3源用于合成 2-(三氟甲基)喹唑啉-4-酮和 4-(三氟甲基)吡咯并/吲哚并[1,2- a ]喹喔啉的直接方法是，无需任何催化剂或添加剂。报告；以 52%–94% 的收率获得了范围广泛的含氟化合物。
• Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines as new antiplasmodial agents
  作者：Nicolas Primas、Peggy Suzanne、Pierre Verhaeghe、Sébastien Hutter、Charline Kieffer、Michèle Laget、Anita Cohen、Julie Broggi、Jean-Charles Lancelot、Aurélien Lesnard、Patrick Dallemagne、Pascal Rathelot、Sylvain Rault、Patrice Vanelle、Nadine Azas

  DOI：10.1016/j.ejmech.2014.06.014

  日期：2014.8

  Thanks to a preliminary in vitro screening of several CCl3-substituted-nitrogen containing heterocycles belonging to our chemical library, the 2-trichloromethylquinoxaline scaffold appeared to be of potential interest for developing new antiplasmodial agents. Then, combining these experimental results to the antimalarial properties reported for various pyrrolo[1,2-a]quinoxaline derivatives, an original series of fifteen 7-substituted-4-trichoromethylpyrrolo[1,2-a]quinoxalines was synthesized in a 4 to 5 reaction steps pathway. All molecules were evaluated in vitro toward both their antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were identified, displaying IC50 values in the micromolar range and low cytotoxicity values, reaching good selectivity indexes, in comparison with the reference drugs chloroquine and doxycycline. Structure-activity relationship studies showed that the pyrrolo[1,2-a]quinoxaline scaffold can support selective antiplasmodial activity when substituted at position 4 by a CCl3 group. However, substitution at position 7 of the same scaffold is neither beneficial for cytotoxicity nor favourable for the solubility in the biological media.