2-amino-3-chloro-5-methylquinoxaline | 1275494-82-0

• 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: 2-amino-3-chloro-5-methylquinoxaline
• 英文别名: 3-Chloro-5-methylquinoxalin-2-amine；3-chloro-5-methylquinoxalin-2-amine
• CAS: 1275494-82-0
• 化学式: C₉H₈ClN₃
• 分子量: 193.636
• InChiKey: UUFQAODRNFQREI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-3-chloro-5-methylquinoxaline 在 吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 ethyl N-(3-methoxy-5-methylquinoxalin-2-yl)carbamate
  参考文献：
  名称：

  Synthesis, anticancer activity and pharmacokinetic analysis of 1-[(substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives

  摘要：

  Based on the anticancer activity of novel quinoxalinyl-piperazine compounds, 1-[(5 or 6-substituted alkoxyquinoxalinyl) aminocarbonyl]-4-(hetero) arylpiperazine derivatives published in Bioorg. Med. Chem. 2010, 18, 7966, we further explored the synthesis of 7 or 8-substituted quinoxalinyl piperazine derivatives. From in vitro studies of the newly synthesized compounds using human cancer cell lines, we identified some of the 8-substituted compounds, for example 6p, 6q and 6r, which inhibited the proliferation of various human cancer cells at nanomolar concentrations. Compound 6r, in particular, showed the lowest IC50 values, ranging from 6.1 to 17 nM, in inhibition of the growth of cancer cells, which is better than compound 6k (compound 25 in the reference cited above). In order to select and develop a leading compound among the quinoxaline compounds with substitutions on positions 5, 6, 7 or 8, the compounds comparable to compound 6k in in vitro cancer cell growth inhibition were chosen and their pharmacokinetic properties were evaluated in rats. In these studies, compound 6k showed the highest oral bioavailability of 83.4%, and compounds 6j and 6q followed, with 77.8% and 57.6%, respectively. From the results of in vitro growth inhibitory activities and the pharmacokinetic study, compound 6k is suggested for further development as an orally deliverable anticancer drug. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.026
• 作为产物：
  描述：

  2,3-dichloro-5-methylquinoxaline 在 氨 作用下， 以 二甲基亚砜 为溶剂， 生成 2-amino-3-chloro-5-methylquinoxaline
  参考文献：
  名称：

  Synthesis, anticancer activity and pharmacokinetic analysis of 1-[(substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives

  摘要：

  Based on the anticancer activity of novel quinoxalinyl-piperazine compounds, 1-[(5 or 6-substituted alkoxyquinoxalinyl) aminocarbonyl]-4-(hetero) arylpiperazine derivatives published in Bioorg. Med. Chem. 2010, 18, 7966, we further explored the synthesis of 7 or 8-substituted quinoxalinyl piperazine derivatives. From in vitro studies of the newly synthesized compounds using human cancer cell lines, we identified some of the 8-substituted compounds, for example 6p, 6q and 6r, which inhibited the proliferation of various human cancer cells at nanomolar concentrations. Compound 6r, in particular, showed the lowest IC50 values, ranging from 6.1 to 17 nM, in inhibition of the growth of cancer cells, which is better than compound 6k (compound 25 in the reference cited above). In order to select and develop a leading compound among the quinoxaline compounds with substitutions on positions 5, 6, 7 or 8, the compounds comparable to compound 6k in in vitro cancer cell growth inhibition were chosen and their pharmacokinetic properties were evaluated in rats. In these studies, compound 6k showed the highest oral bioavailability of 83.4%, and compounds 6j and 6q followed, with 77.8% and 57.6%, respectively. From the results of in vitro growth inhibitory activities and the pharmacokinetic study, compound 6k is suggested for further development as an orally deliverable anticancer drug. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.026

文献信息

• Synthesis and anticancer activity of new 1-[(5 or 6-substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives
  作者：Young Bok Lee、Young-Dae Gong、Heejeong Yoon、Chang-Ho Ahn、Moon-Kook Jeon、Jae-Yang Kong

  DOI：10.1016/j.bmc.2010.09.028

  日期：2010.11.15

  A series of novel quinoxalinyl-piperazine compounds, 1-[(5 or 6-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives were synthesized and evaluated as an anticancer agent. From screening of quinoxalinyl-piperazine compound library, we identified that many compounds inhibited proliferation of various human cancer cells at nanomolar concentrations. Among them, one of the fluoro quinoxalinyl-piperazine derivatives showed its IC(50) values ranging from 11 to 21 nM in the growth inhibition of cancer cells. This compound also displayed a more potent effect than paclitaxel against paclitaxel resistant HCT-15 colorectal carcinoma cells. The potency of this novel compound was further confirmed with the synergistic cytotoxic effect with several known cancer drugs such as paclitaxel, doxorubicin, cisplatin, gemcitabine or 5-fluorouracil in cancer cells. This strong cell killing effect was derived from the induction of apoptosis. Mechanistic studies have shown that this quinoxalinyl-piperazine compound is a G2/M-specific cell cycle inhibitor and inhibits anti-apoptotic Bcl-2 protein with p21 induction. Thus the results suggest that our compound has potential use in the growth inhibition of drug resistant cancer cells and the combination therapy with other clinically approved anticancer agents as well. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis, anticancer activity and pharmacokinetic analysis of 1-[(substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives
  作者：Young Bok Lee、Young-Dae Gong、Deog Joong Kim、Chang-Ho Ahn、Jae-Yang Kong、Nam-Sook Kang

  DOI：10.1016/j.bmc.2011.12.026

  日期：2012.2

  Based on the anticancer activity of novel quinoxalinyl-piperazine compounds, 1-[(5 or 6-substituted alkoxyquinoxalinyl) aminocarbonyl]-4-(hetero) arylpiperazine derivatives published in Bioorg. Med. Chem. 2010, 18, 7966, we further explored the synthesis of 7 or 8-substituted quinoxalinyl piperazine derivatives. From in vitro studies of the newly synthesized compounds using human cancer cell lines, we identified some of the 8-substituted compounds, for example 6p, 6q and 6r, which inhibited the proliferation of various human cancer cells at nanomolar concentrations. Compound 6r, in particular, showed the lowest IC50 values, ranging from 6.1 to 17 nM, in inhibition of the growth of cancer cells, which is better than compound 6k (compound 25 in the reference cited above). In order to select and develop a leading compound among the quinoxaline compounds with substitutions on positions 5, 6, 7 or 8, the compounds comparable to compound 6k in in vitro cancer cell growth inhibition were chosen and their pharmacokinetic properties were evaluated in rats. In these studies, compound 6k showed the highest oral bioavailability of 83.4%, and compounds 6j and 6q followed, with 77.8% and 57.6%, respectively. From the results of in vitro growth inhibitory activities and the pharmacokinetic study, compound 6k is suggested for further development as an orally deliverable anticancer drug. (C) 2011 Elsevier Ltd. All rights reserved.