(S)-N-(4-hydroxybenzyl)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxamide

• 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: (S)-N-(4-hydroxybenzyl)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxamide
• 英文别名: (1S)-N-[(4-hydroxyphenyl)methyl]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxamide
• 化学式: C₁₉H₁₉N₃O₂
• 分子量: 321.379
• InChiKey: BNFGDXCADGZDPA-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  64.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (S)-(+)-1-(2-nitro-benzyl)-5-oxopyrrolidine-2-carboxylic acid 在 iron(III) chloride hexahydrate 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 甲烷 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (S)-N-(4-hydroxybenzyl)-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

文献信息

• 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.