N-benzyl-2-((2-hydroxy-3-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propyl)(methyl)amino)acetamide | 1428961-92-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-benzyl-2-((2-hydroxy-3-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propyl)(methyl)amino)acetamide
• 英文别名: N-benzyl-2-[[2-hydroxy-3-(1-methyl-2,4-dioxo-quinazolin-3-yl)propyl]-methyl-amino]acetamide；N-benzyl-2-[[2-hydroxy-3-(1-methyl-2,4-dioxoquinazolin-3-yl)propyl]-methylamino]acetamide
• CAS: 1428961-92-5
• 化学式: C₂₂H₂₆N₄O₄
• 分子量: 410.473
• InChiKey: QHKJWVBGETUIQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyl-2-((2-hydroxy-3-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propyl)(methyl)amino)acetamide 在 盐酸 作用下， 以 乙腈 为溶剂， 生成 N-benzyl-2-((2-hydroxy-3-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propyl)(methyl)amino)acetamide hydrochloride
  参考文献：
  名称：

  Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents

  摘要：

  A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by H-1 NMR, C-13 NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 51, and So had strong inhibitory potency against CHS. Compound 5c, which has the highest potency among these compounds, had a half-inhibition concentration (IC50) of 0.08 mmol/L, while polyoxin B as positive drug had IC50 of 0.18 mmol/L. These IC50 values of compounds 5i, 5m, 5n, and Ss were greater than 0.75 mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus, the activities of 5g, 51 and 50 were 16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans, the minimum-inhibition-concentration (MIC) values of compounds 5c, 5d, Se and 51 were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.042
• 作为产物：
  描述：

  1-甲基-2,4(1h,3h)-喹唑啉二酮 在 potassium carbonate 、 sodium sulfate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.0h， 生成 N-benzyl-2-((2-hydroxy-3-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)propyl)(methyl)amino)acetamide
  参考文献：
  名称：

  Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents

  摘要：

  A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by H-1 NMR, C-13 NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 51, and So had strong inhibitory potency against CHS. Compound 5c, which has the highest potency among these compounds, had a half-inhibition concentration (IC50) of 0.08 mmol/L, while polyoxin B as positive drug had IC50 of 0.18 mmol/L. These IC50 values of compounds 5i, 5m, 5n, and Ss were greater than 0.75 mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus, the activities of 5g, 51 and 50 were 16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans, the minimum-inhibition-concentration (MIC) values of compounds 5c, 5d, Se and 51 were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.042

文献信息

• Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents
  作者：Qinggang Ji、Dan Yang、Xin Wang、Chunyan Chen、Qiao Deng、Zhiqiang Ge、Lvjiang Yuan、Xiaolan Yang、Fei Liao

  DOI：10.1016/j.bmc.2014.04.042

  日期：2014.7

  A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by H-1 NMR, C-13 NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 51, and So had strong inhibitory potency against CHS. Compound 5c, which has the highest potency among these compounds, had a half-inhibition concentration (IC50) of 0.08 mmol/L, while polyoxin B as positive drug had IC50 of 0.18 mmol/L. These IC50 values of compounds 5i, 5m, 5n, and Ss were greater than 0.75 mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus, the activities of 5g, 51 and 50 were 16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans, the minimum-inhibition-concentration (MIC) values of compounds 5c, 5d, Se and 51 were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents. (C) 2014 Elsevier Ltd. All rights reserved.