(S)-(-)-7-bromo-1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazoline-1-carboxylic acid | 1198424-22-4

• 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: (S)-(-)-7-bromo-1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazoline-1-carboxylic acid
• 英文别名: (1S)-7-bromo-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid
• CAS: 1198424-22-4
• 化学式: C₁₂H₁₁BrN₂O₂
• 分子量: 295.136
• InChiKey: XHPHQHXABUWOQD-JTQLQIEISA-N

物化性质

• 熔点：
  282.5-284.9 °C
• 沸点：
  493.3±55.0 °C(predicted)
• 密度：
  1.81±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对羟基苯乙胺 、 (S)-(-)-7-bromo-1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazoline-1-carboxylic acid 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 以43.8%的产率得到(S)-7-bromo-N-(4-hydroxyphenethyl)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxamide
  参考文献：
  名称：

  Design, synthesis and bioevaluation of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives as potent neuroprotective agents

  摘要：

  Diverse of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives were designed, synthesized and evaluated for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, and 5q exhibited excellent neuroprotective activity. The compound 5q was selected for further investigation. We found that 5q could attenuate Ca2+ influx induced by NMDA, meanwhile, Sq could suppress the NR2B up-regulation and increase p-ERK1/2 expression. The molecular docking results showed that 5q might fit well in the binding pocket of 4 and interact with some key residues in the binding pocket of 1 simultaneously. Besides, 5q exhibited acceptable metabolic stability. These results suggested that 5q was a promising lead for further development of new potent and orally bioavailable NR2B-selective NMDAR antagonists. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.052
• 作为产物：
  描述：

  5-溴-2-硝基苯甲醛 在 乙二胺 、 iron(III) chloride hexahydrate 、 甲烷 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 80.5h， 生成 (S)-(-)-7-bromo-1,2,3,9-tetrahydropyrrolo[2,1-b]-quinazoline-1-carboxylic acid
  参考文献：
  名称：

  新型 NR2B 选择性 NMDAR 拮抗剂的鉴定和硅结合研究

  摘要：

  阿尔茨海默病（AD）是威胁人类健康的一大类疾病，对其药物和治疗方法的探索从未停止。NMDA 受体拮抗剂作为潜在治疗靶点的研究和开发也一直在进行中。我们小组基于 NR2B-NMDARs 靶标设计合成了 22 种新的四氢吡咯并[2,1– b ]喹唑啉，并评估了它们在体外对 NMDA 诱导的细胞毒性的神经保护活性，A21 表现出优异的神经保护活性。随后，四氢吡咯并 [2,1– b]的构效关系和抑制剂结合模式]喹唑啉通过分子对接、分子动力学 (MD) 模拟和结合自由能计算进一步分析。结果显示A21可以匹配NR2B-NMDARs的两个结合口袋。本项目的研究成果将为新型NR2B-NMDA受体拮抗剂的研究奠定一定的基础，也为该靶点的后续研发提供新的思路。

  DOI：

  10.1016/j.bmcl.2023.129213

文献信息

• Synthesis and Biological Evaluation of (−)-Linarinic Acid Derivatives as Neuroprotective Agents against OGD-Induced Cell Damage
  作者：Yu Tian、Chao Ma、Linyin Feng、Lei Zhang、Feiyue Hao、Li Pan、Maosheng Cheng

  DOI：10.1002/ardp.201100424

  日期：2012.6

  A series of novel (−)‐1,2,3,9‐tetrahydropyrrolo[2,1‐b]quinazoline‐1‐carboxylic acid derivatives were designed and synthesized. All of the prepared compounds were screened for their neuroprotective effects using an in vitro oxygen glucose deprivation (OGD) model of ischemic stroke. Some of the target compounds exhibited moderate to excellent protective potency. In particular, compounds 9d, 9e, 9g, and

  设计并合成了一系列新型 (-)-1,2,3,9-四氢吡咯并[2,1-b]喹唑啉-1-羧酸衍生物。使用缺血性中风的体外氧糖剥夺 (OGD) 模型筛选所有制备的化合物的神经保护作用。一些目标化合物表现出中等至优异的保护效力。特别是，化合物 9d、9e、9g 和 9h 在所有三种测试浓度下都对 SH-SY5Y 细胞系显示出显着的保护作用。
• Design, synthesis and bioevaluation of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives as potent neuroprotective agents
  作者：Linkui Zhang、Ying Zhao、Jian Wang、Donglin Yang、Chenwen Zhao、Changli Wang、Chao Ma、Maosheng Cheng

  DOI：10.1016/j.ejmech.2018.03.052

  日期：2018.5

  Diverse of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives were designed, synthesized and evaluated for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, and 5q exhibited excellent neuroprotective activity. The compound 5q was selected for further investigation. We found that 5q could attenuate Ca2+ influx induced by NMDA, meanwhile, Sq could suppress the NR2B up-regulation and increase p-ERK1/2 expression. The molecular docking results showed that 5q might fit well in the binding pocket of 4 and interact with some key residues in the binding pocket of 1 simultaneously. Besides, 5q exhibited acceptable metabolic stability. These results suggested that 5q was a promising lead for further development of new potent and orally bioavailable NR2B-selective NMDAR antagonists. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Identification and in silicon binding study of a novel NR2B selective NMDAR antagonist
  作者：Chen Yang、Hanxun Wang、Jin Yang、Yue Zhang、Fengyun Qin、Yeli He、Jiao Liu、Chao Ma、Maosheng Cheng

  DOI：10.1016/j.bmcl.2023.129213

  日期：2023.4

  never stopped. Research and development of NMDA receptor antagonists as potential therapeutic targets have also been ongoing. Our group designed and synthesized 22 new tetrahydropyrrolo[2,1–b]quinazolines based on NR2B-NMDARs targets and evaluated them for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, A21 exhibited excellent neuroprotective activity. Subsequently, the structure–activity

  阿尔茨海默病（AD）是威胁人类健康的一大类疾病，对其药物和治疗方法的探索从未停止。NMDA 受体拮抗剂作为潜在治疗靶点的研究和开发也一直在进行中。我们小组基于 NR2B-NMDARs 靶标设计合成了 22 种新的四氢吡咯并[2,1– b ]喹唑啉，并评估了它们在体外对 NMDA 诱导的细胞毒性的神经保护活性，A21 表现出优异的神经保护活性。随后，四氢吡咯并 [2,1– b]的构效关系和抑制剂结合模式]喹唑啉通过分子对接、分子动力学 (MD) 模拟和结合自由能计算进一步分析。结果显示A21可以匹配NR2B-NMDARs的两个结合口袋。本项目的研究成果将为新型NR2B-NMDA受体拮抗剂的研究奠定一定的基础，也为该靶点的后续研发提供新的思路。