3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-oxopropanenitrile | 357284-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-oxopropanenitrile
• 英文别名: 3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-oxopropanenitrile；3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-3-oxo-propionitrile
• CAS: 357284-86-7
• 化学式: C₁₁H₉NO₃
• mdl: MFCD09745922
• 分子量: 203.197
• InChiKey: POGKLPJUZGOSPG-UHFFFAOYSA-N

物化性质

• 熔点：
  168-170 °C
• 沸点：
  421.1±45.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-oxopropanenitrile 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以62%的产率得到5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-pyrazol-3-amine
  参考文献：
  名称：

  Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

  摘要：

  FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV411 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.021
• 作为产物：
  描述：

  6-乙酰基-1,4-苯并二氧杂环 在 copper(ll) bromide 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-oxopropanenitrile
  参考文献：
  名称：

  双级抗疟唑并[3,4-b]吡啶的合成及其构效关系。

  摘要：

  疟疾仍然是最致命的传染病之一，每年导致成千上万的死亡，主要是在幼儿和孕妇中。在这里，我们报道了针对恶性疟原虫（疟疾最致命的物种）的一系列吡唑并[3,4- b ]吡啶的发现和衍生化。该系列中的命中化合物在体外显示出亚微摩尔对寄生虫的红细胞内阶段具有高活性，对人成纤维细胞BJ和肝HepG2细胞系几乎没有毒性。此外，我们的命中化合物对寄生虫的肝期表现出良好的活性，但对配子体阶段的活性却很小。包括杀死率，对接率和分子动力学研究在内的寄生虫学资料表明，我们的化合物可能靶向细胞色素bc 1的Q o结合位点。

  DOI：

  10.1021/acs.jmedchem.0c01152

文献信息

• Adenosine receptor ligands and their use in the treatment of disease
  申请人：——

  公开号：US20010027196A1

  公开（公告）日：2001-10-04

  The invention relates to cyclic heteroaromatic compounds, containing at least one nitrogen atom, and to their use in the manufacture of medicaments for the treatment of diseases, related to adenosine receptor modulators, such as Alzheimer's disease, Parkinson's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure, substance abuse, sedation and they may be active as muscle relaxants, antipsychotics, anti epileptics, anticonvulsants and cardiaprotective agents.

  这项发明涉及含有至少一个氮原子的环状杂芳化合物，以及它们在制造用于治疗与腺苷受体调节剂相关的疾病的药物中的应用，如阿尔茨海默病、帕金森病、神经保护、精神分裂症、焦虑、疼痛、呼吸功能障碍、抑郁症、哮喘、过敏反应、缺氧、缺血、癫痫、物质滥用、镇静，它们可能作为肌肉松弛剂、抗精神病药、抗癫痫药、抗惊厥药和心脏保护剂而具有活性。
• PREPARATION OF PYRAZOLO[3,4-B]PYRIDINES AS ANTIMALARIALS
  申请人：University of Kentucky Research Foundation

  公开号：US20210101901A1

  公开（公告）日：2021-04-08

  The present invention relates to pyrazolo[3,4-b]pyridine compounds. The present invention further relates to methods for inhibiting Plasmodium comprising contacting Plasmodium with pyrazolo[3,4-b]pyridine compounds described herein. Also described herein are methods of treating malaria comprising administering pyrazolo[3,4-b]pyridine compounds to a subject in need thereof.

  本发明涉及吡唑并[3,4-b]吡啶化合物。本发明还涉及一种抑制疟原虫的方法，包括将疟原虫与本文描述的吡唑并[3,4-b]吡啶化合物接触。本文还描述了一种治疗疟疾的方法，包括向需要的受试者施用吡唑并[3,4-b]吡啶化合物。
• ADENOSINE RECEPTOR MODULATORS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1261327A2

  公开（公告）日：2002-12-04
• US6586441B2
  申请人：——

  公开号：US6586441B2

  公开（公告）日：2003-07-01
• [EN] ADENOSINE RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RECEPTEURS DE L'ADENOSINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2001062233A2

  公开（公告）日：2001-08-30

  The invention relates to cyclic heteroaromatic compounds, containing at least one nitrogen atom, and to their use in the manufacture of medicaments for the treatment of diseases, related to adenosine receptor modulators, such as Alzheimer's disease, Parkinson's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, asthma, allergic responses, hypoxia, ischaemia, seizure, substance abuse, sedation and they may be active as muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardioprotective agents.