2,3-dimorpholino-6-nitroquinoxaline | 158438-60-9

• 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: 2,3-dimorpholino-6-nitroquinoxaline
• 英文别名: 4,4'-(6-nitroquinoxaline-2,3-diyl)dimorpholine；4-(3-Morpholin-4-yl-6-nitroquinoxalin-2-yl)morpholine
• CAS: 158438-60-9
• 化学式: C₁₆H₁₉N₅O₄
• 分子量: 345.358
• InChiKey: LHDKFHKPKKHJDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,3-dimorpholino-6-nitroquinoxaline 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 6-(bromoacetyl)amino-2,3-dimorpholinoquinoxaline
  参考文献：
  名称：

  Synthesis of 6-(Bromoacetyl)amino-2,3-dimorpholinoquinoxaline and Application to a New Fluorescence Derivatization Reagent of Fatty Acids for the High-Performance Liquid Chromatographic Analysis

  摘要：

  6-Amino-2,3-dimorpholinoquinoxaline (3) was allowed to react with bromoacetic acid in the presence of DCC to give 6-(bromoacetyl)amino-2,3-dimorpholinoquinoxaline (4). Five kinds of saturated fatty acids (C-10, C-12, C-14, C-16, and C-18) were subjected to the derivatization with compound (4) within 50 min to afford the corresponding fluorescent products (5a-e). All the peaks of the derivatized products clearly separated within 15 min. The detection limit of decanoic acid (C-10) was estimated to be 10 fmol/10 mu L injection volume (S/N=4).

  DOI：

  10.3987/com-98-s(h)47
• 作为产物：
  描述：

  6-硝基-2,3-二羟基喹喔啉 在 caesium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2,3-dimorpholino-6-nitroquinoxaline
  参考文献：
  名称：

  Design and Synthesis of Small Molecule RhoA Inhibitors: A New Promising Therapy for Cardiovascular Diseases?

  摘要：

  RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromolecules, and to our knowledge, small molecular-based inhibitors have not been reported. In this study, a series of first-in-class small molecular RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. Virtual screening of similar to 200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level (compounds 1-3). Compound 1 was selected for further structure modifications in considering binding activity and synthesis ease. Fourty-one new compounds (1, 12a-v, 13a-h, and 14a-j) were designed and synthesized accordingly. It was found that eight (12a, 12j, 14a, 14b, 14d, 14e, 14 g, and 14h) showed high RhoA inhibition activities with IC(50) values of 1.24 to 3.00 mu M. A pharmacological assay indicated that two compounds (14g and 14 h) demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.

  DOI：

  10.1021/jm200161c

文献信息

• Synthesis of 2,3-Disubstituted 6-Aminoquinoxalines and Their Application to New Fluorescence Derivatization Reagents for Carboxylic Acids
  作者：Akira Katoh、Motoki Takahashi、Junko Ohkanda

  DOI：10.1246/cl.1996.369

  日期：1996.5

  Fluorescent 2,3-disubstituted 6-aminoquinoxalines were synthesized by reaction of 2,3-dichloro-6-nitroquinoxaline with some nucleophiles and subsequent catalytic hydrogenation of the nitro group. Further, two of them were demonstrated to be new high-sensitive fluorescence derivatization reagents (1 fmol/1 μl injection volume) for long-chain carboxylic acids.

  通过 2,3-二氯-6-硝基喹喔啉与一些亲核物反应，然后催化硝基氢化，合成了荧光 2,3-二取代 6-氨基喹喔啉。此外，研究还证明其中两种化合物是长链羧酸的新型高灵敏度荧光衍生试剂（1 fmol/1 μl进样量）。
• Design and Synthesis of Small Molecule RhoA Inhibitors: A New Promising Therapy for Cardiovascular Diseases?
  作者：Jing Deng、Enguang Feng、Sheng Ma、Yan Zhang、Xiaofeng Liu、Honglin Li、Huang Huang、Jin Zhu、Weiliang Zhu、Xu Shen、Liyan Miao、Hong Liu、Hualiang Jiang、Jian Li

  DOI：10.1021/jm200161c

  日期：2011.7.14

  RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. However, to date, RhoA inhibitors are macromolecules, and to our knowledge, small molecular-based inhibitors have not been reported. In this study, a series of first-in-class small molecular RhoA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. Virtual screening of similar to 200,000 compounds, followed by SPR-based binding affinity assays resulted in three compounds with binding affinities to RhoA at the micromolar level (compounds 1-3). Compound 1 was selected for further structure modifications in considering binding activity and synthesis ease. Fourty-one new compounds (1, 12a-v, 13a-h, and 14a-j) were designed and synthesized accordingly. It was found that eight (12a, 12j, 14a, 14b, 14d, 14e, 14 g, and 14h) showed high RhoA inhibition activities with IC(50) values of 1.24 to 3.00 mu M. A pharmacological assay indicated that two compounds (14g and 14 h) demonstrated noticeable vasorelaxation effects against PE-induced contraction in thoracic aorta artery rings and served as good leads for developing more potent cardiovascular agents.
• Synthesis of 6-(Bromoacetyl)amino-2,3-dimorpholinoquinoxaline and Application to a New Fluorescence Derivatization Reagent of Fatty Acids for the High-Performance Liquid Chromatographic Analysis
  作者：Akira Katoh、Takeshi Fujimoto、Motoki Takahashi、Junko Ohkanda

  DOI：10.3987/com-98-s(h)47

  日期：——

  6-Amino-2,3-dimorpholinoquinoxaline (3) was allowed to react with bromoacetic acid in the presence of DCC to give 6-(bromoacetyl)amino-2,3-dimorpholinoquinoxaline (4). Five kinds of saturated fatty acids (C-10, C-12, C-14, C-16, and C-18) were subjected to the derivatization with compound (4) within 50 min to afford the corresponding fluorescent products (5a-e). All the peaks of the derivatized products clearly separated within 15 min. The detection limit of decanoic acid (C-10) was estimated to be 10 fmol/10 mu L injection volume (S/N=4).