6-fluoro-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-9-one

• 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: 6-fluoro-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-9-one
• 英文别名: 6-fluoro-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one
• 化学式: C₁₁H₉FN₂O
• 分子量: 204.204
• InChiKey: VEWATDYGGXXZDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-fluoro-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-9-one 在 三甲基氯硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (E)-6-((2-(diethylamino)ethyl)amino)-3-(4-isopropylbenzylidene)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of New Quinazolinone Derivatives that Inhibit Bloom Syndrome Protein (BLM) Helicase, Trigger DNA Damage at the Telomere Region, and Synergize with PARP Inhibitors

  摘要：

  DNA damage response (DDR) pathways are crucial for the survival of cancer cells and are attractive targets for cancer therapy. Bloom syndrome protein (BLM) is a DNA helicase that performs important roles in DDR pathways. Our previous study discovered an effective new BLM inhibitor with a quinazolinone scaffold by a screening assay. Herein, to better understand the structure-activity relationship (SAR) and biological roles of the BLM inhibitor, a series of new derivatives were designed, synthesized, and evaluated based on this scaffold. Among them, compound 9h exhibited nanomolar inhibitory activity and binding affinity for BLM. 9h could effectively disrupt BLM recruitment to DNA in cells. Furthermore, 9h inhibited the proliferation of the colorectal cell line HCT116 by significantly triggering DNA damage in the telomere region and inducing apoptosis, especially in combination with a poly (ADP-ribose) polymerase (PARP) inhibitor. This result suggested a synthetic lethal effect between the BLM and PARP inhibitors in DDR pathways.

  DOI：

  10.1021/acs.jmedchem.0c00917
• 作为产物：
  描述：

  N-BOC-GAMMA-氨基丁酸 、 2-氨基-4-氟苯甲酸 在 吡啶 、 亚磷酸三苯酯 作用下， 反应 0.17h， 以49%的产率得到6-fluoro-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-9-one
  参考文献：
  名称：

  微波辐射促进了新的一锅全合成的脱氧vasicinone，麦金唑啉酮，isaindigotone及其衍生物。

  摘要：

  [反应：请参见文字]。通过新型的微波辅助多米诺反应合成脱氧维西酮（1），麦金唑啉酮（2）和8-羟基脱氧维西酮（3）以及通过微波辐射促进的新的三组分一锅异靛酮的全合成（5） ，均已报告。高效的反应过程使我们能够快速获取相关的天然产物衍生物，并鉴定出一类新的细胞毒剂。

  DOI：

  10.1021/ol0513084

文献信息

• Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents
  作者：Kangjia Du、Wantong Ma、Chengjie Yang、Zhongkun Zhou、Shujian Hu、Yanan Tian、Hao Zhang、Yunhao Ma、Xinrong Jiang、Hongmei Zhu、Huanxiang Liu、Peng Chen、Yingqian Liu

  DOI：10.1080/14756366.2022.2065672

  日期：2022.12.31

  concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The

  摘要 合成了一系列来自isaits indigotone 的新型衍生物 isaits indigotone 的根（化合物1 – 26）。四种人胃肠道癌细胞（HCT116、PANC-1、SMMC-7721 和 AGS）用于评估抗增殖活性。其中，化合物6对AGS细胞表现出最有效的抑制活性，IC 50（50%抑制浓度）值为2.2 μM。潜在机制研究表明化合物6诱导AGS细胞凋亡。证明了 AGS 细胞中线粒体膜电位 (MMP) 的崩溃。在对接分析中，化合物6之间具有良好的亲和相互作用并发现了 AKT1。用化合物6处理 AGS 细胞也导致 PI3K/AKT/mTOR 信号通路的显着抑制。MMP 的崩溃和 PI3K/AKT/mTOR 信号通路的抑制可能是诱导细胞凋亡的原因。该衍生物化合物6可用作治疗胃癌的潜在抗肿瘤剂。
• 7 8 9 10-tetrahydro-6h-azepino, 6 7 8 9-tetrahydro-pyrido and 2 3-dihydro-2h-pyrrolo[2 1-b]-quinazolinone derivates
  申请人：Aissaoui Hamed

  公开号：US20050009852A1

  公开（公告）日：2005-01-13

  The invention relates to novel 7,8,9,10-tetrahydro-6H-azepino, 6,7,8,9-tetrahydro-pyrido and 2,3-dihydro-2H-pyrrolo[2, 1-b]-quinazolinone derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.

  本发明涉及新的7,8,9,10-四氢-6H-氮杂环[4,3,2-de] [1,4]苯并，6,7,8,9-四氢-吡啶和2,3-二氢-2H-吡咯[2,1-b]喹唑啉衍生物的制备方法，以及这些化合物作为药物组分在制备药物组合物中的应用。本发明还涉及相关方面，包括制备这些化合物的过程，含有这些化合物中的一个或多个的药物组合物，特别是它们作为促进睡眠的药物的用途。
• 7,8,9,10-TETRAHYDRO-6H-AZEPINO, 6,7,8,9-TETRAHYDRO-PYRIDO AND 2,3-DIHYDRO-2H-PYRROLO (2,1-B)-QUINAZOLINONE DERIVATIVES
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1521583B1

  公开（公告）日：2007-01-10
• US7067519B2
  申请人：——

  公开号：US7067519B2

  公开（公告）日：2006-06-27