咪唑并[1,5-a]喹喔啉-4(5H)-酮 | 179042-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 咪唑并[1,5-a]喹喔啉-4(5H)-酮
• 中文别名: 羊毛甾-7,9(11),20-三烯-3b,18-二醇,二乙酸酯(8CI)
• 英文名称: imidazo[1,5-a]quinoxalin-4(5H)-one
• 英文别名: 5H-imidazo[1,5-a]quinoxalin-4-one
• CAS: 179042-26-3
• 化学式: C₁₀H₇N₃O
• mdl: MFCD18833354
• 分子量: 185.185
• InChiKey: JYZUDVSNYNWXHM-UHFFFAOYSA-N

物化性质

• 沸点：
  289.8±9.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  咪唑并[1,5-a]喹喔啉-4(5H)-酮 在 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 0.75h， 生成 N-methylimidazo[1,5-a]quinoxalin-4-amine
  参考文献：
  名称：

  咪唑并[1,2- a ]吡嗪，咪唑并[1,5- a ]喹喔啉和吡唑并[1,5- a ]喹喔啉衍生物作为IKK1和IKK2抑制剂

  摘要：

  转录核因子NF-κB在慢性和急性炎症性疾病中起关键作用。在抑制NF-κB的几种不同策略中，IKK抑制剂的开发似乎是制药业考虑的最有效方法之一。在以前的研究中，在一系列咪唑并[1,2- a ]喹喔啉衍生物中突出了两种潜在的IKK2抑制剂。为了增强该活性，我们在此提出基于咪唑并[1,2- a ]吡嗪，咪唑并[1,5- a ]喹喔啉或吡唑并[1,5- a ]喹喔啉的二十一种新化合物的合成。结构。还测试了它们抑制IKK1和IKK2活性的潜力。

  DOI：

  10.1016/j.ejmech.2017.07.021
• 作为产物：
  描述：

  N-Boc-1,2-亚苯基二胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 0.34h， 生成 咪唑并[1,5-a]喹喔啉-4(5H)-酮
  参考文献：
  名称：

  A Van Leusen deprotection-cyclization strategy as a fast entry into two imidazoquinoxaline families

  摘要：

  A concise synthesis of two pharmacologically relevant classes of molecules possessing the imidazoquinoxaline core is reported. The protocol involves use of 1,2-phenylenediamines and glyoxylic acid derivatives, namely ethyl glyoxylate or benzylglyoxamide, along with tosylmethylisocyanides in a microwave-assisted Van Leusen three-component condensation. Subsequent unmasking (Boc removal) of an internal amino-nucleophile promotes deprotection and cyclization that take place either spontaneously in a one-pot fashion to give 8 or upon acidic treatment under microwave irradiation after isolation of the imidazole intermediate to give 11. Of note, a tricyclic framework is hence assembled by means of a rapid and straightforward method with a high bond-forming efficiency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.08.072

文献信息

• Synthesis of imidazo[1,5-a]quinoxalin-4(5H)-one template via a novel intramolecular cyclization process
  作者：Derek Norris、Ping Chen、Joel C Barrish、Jagabandhu Das、Robert Moquin、Bang-Chi Chen、Peng Guo

  DOI：10.1016/s0040-4039(01)00698-0

  日期：2001.6

  A novel, efficient, and regiospecific method for the construction of the imidazo[1,5-a]quinoxalin-4(5H)-one template is described. The key reaction involves an intramolecular cyclization process and provides the desired products in excellent yield.

  描述了一种新颖，有效且针对区域的方法，用于构建咪唑并[1,5 - a ]喹喔啉-4（5 H）-one模板。关键反应涉及分子内环化过程，并以优异的产率提供所需的产物。
• QUINOXALINE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP2615096A1

  公开（公告）日：2013-07-17

  [Problem] Provided is a compound which has a PDE9-inhibitory action and is useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, and bladder/urethral diseases, and the like. [Means for Solution] The present inventors have investigated a compound which has a PDE9-inhibitory action and is useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, and bladder/urethral diseases, and the like, and thus, have found that an imidazoquinoxaline compound or a triazoloquinoxaline compound has a PDE9-inhibitory action, thereby completing the present invention. The imidazoquinoxaline compound or the triazoloquinoxaline compound of the present invention has a PDE9-inhibitory action and can be used as an agent for preventing and/or treating storage dysfunction, voiding dysfunction, and bladder/urethral diseases, and the like.

  问题 本发明提供了一种化合物，该化合物具有 PDE9 抑制作用，可用作治疗和/或预防储藏功能障碍、排尿功能障碍和膀胱/尿道疾病等药物的活性成分。 [解决方法］ 本发明人研究了一种具有 PDE9 抑制作用且可作为治疗和/或预防储藏功能障碍、排尿功能障碍和膀胱/尿道疾病等药物的活性成分的化合物，并因此发现咪唑喹喔啉化合物或三唑喹喔啉化合物具有 PDE9 抑制作用，从而完成了本发明。本发明的咪唑喹喔啉化合物或三唑喹喔啉化合物具有 PDE9 抑制作用，可用作预防和/或治疗储藏功能障碍、排尿功能障碍和膀胱/尿道疾病等的制剂。
• [EN] 3-SUBSTITUTED IMIDAZO(1,5-A)QUINOXALINES AND QUINAZOLINES WITH CNS ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：WO1993017025A1

  公开（公告）日：1993-09-02

  (EN) A 4-oxoimidazo(1,5-a)quinoxaline of formula (I), a 5-oxoimadazo(1,5-a)quinoxaline of formula (II), a diimidazoquinazoline of formula (III) or a pharmaceutically acceptable salt thereof, wherein R3 is (a), (b), (c), (d). The R-groups and 'Aryl' are as defined herein. The compounds are useful in the treatment of central nervous system disorders associated with the benzodiazepine receptors in a subject in need of such treatment comprising administering to the subject a therapeutically-effective amount of formula (I), (II) or (III) compound for alleviation of such disorder. Typically, the compound of formula (I), (II) or (III) is administered in the form of a pharmaceutical composition comprising a pharmaceutically-acceptable carrier or diluent.(FR) 4-oxoimidazo(1,5-a)quinoxaline de la formule (I), 5-oxoimidazo(1,5-a)quinoxaline de la formule (II), diimidazoquinazoline de la formule (III), ou sel pharmaceutiquement acceptable de ces composés, R3 représentant (a), (b), (c), (d). Les groupes R et 'Aryle' sont tels que définis dans le descriptif. Ces composés peuvent être utilisés pour le traitement d'affections du système nerveux central associées aux récepteurs de benzodiazépine chez un patient, le traitement consistant à administrer au patient une dose thérapeutique efficace d'un composé de la formule (I), (II) ou (III) permettant d'en soulager les symptômes. Généralement, le composé de la formule (I), (II) ou (III) est administré sous la forme d'une composition pharmaceutique comprenant un diluant ou un excipient pharmaceutiquement acceptables.

  （EN）一种4-oxoimidazo(1,5-a)quinoxaline（I），5-oxoimadazo(1,5-a)quinoxaline（II），二imidazoquinazoline（III）或其他的药理学上可接受的盐类。其中R3为(a)，(b)，(c)，(d)。R基团和“Aryl”如同文所述定义。这些化合物在治疗中枢神经系统障碍中与苯丁likediazepine受体相关的疾病中（需要接受这种治疗的患者）有治疗活性，方法是给患者注射治疗有效量的化合物（I）、（II）或（III）以减轻这方面的症状。通常情况下，化合物（I）、（II）或（III）是在一种药理学上可接受的载体或稀释剂的药剂形式下消费的。（FR）一种4-oxoimidazo(1,5-a)quinoxaline（I），一种5-oxoimadazo(1,5-a)quinoxaline（II），一种二imidazoquinazoline（III），或药理学上来说，它们的盐类，其中R3代表（a）到（d）。R支链体和“Aryl”如同文所述这样定义。这些化合物可用在治疗中枢神经系统障碍，而这种障碍是与苯丁likediazepine受体相关的系统性的症状需要治疗的患者那里，治疗疗效可用给患者注射治疗有效量的（I）、（II）或（III）以减轻症状。通常，化合物（I）、（II）或（III）以一种在药剂学上可用的载体或稀释剂的药剂形式给出。
• In vitro and in vivo anti-tumoral activities of imidazo[1,2-a]quinoxaline, imidazo[1,5-a]quinoxaline, and pyrazolo[1,5-a]quinoxaline derivatives
  作者：Georges Moarbess、Carine Deleuze-Masquefa、Vanessa Bonnard、Stéphanie Gayraud-Paniagua、Jean-Rémi Vidal、Françoise Bressolle、Frédéric Pinguet、Pierre-Antoine Bonnet

  DOI：10.1016/j.bmc.2008.05.022

  日期：2008.7.1

  Imidazoquinoxaline and pyrazoloquinoxaline derivatives, analogues of imiquimod, were synthesized, and their in vitro cytotoxic and pharmacodynamic activities were evaluated. In vitro cytotoxicity studies were assessed against melanoma (A375, M4Be, RPMI-7591), colon (LS174T), breast (MCF7), and lymphoma (Raji) human cancer cell lines. In vivo studies were carried out in M4Be xenografted athymic mice. EAPB0103, EAPB0201, EAPB0202, and EAPB0203 showed significant in vitro activities against A375 compared to fotemustine and imiquimod used as references. These compounds were 6-110 and 2-45 times more active than fotemustine and imiquimod, respectively. EAPB0203 bearing phenethyl as substituent at position 1 and methylamine at position 4 showed the highest activity. EAPB0203 has also a more potent cytotoxic activity than imiquimod and fotemustine in M4Be and RPMI-7591 and interesting cytotoxic activity in other tumor cell lines tested. In vivo, EAPB0203 treatment schedules caused a significant decrease in tumor size compared to vehicle control and fotemustine treatments. (c) 2008 Elsevier Ltd. All rights reserved.
• Reaction of quinoxalin-2-ones with TosMIC reagent: synthesis of imidazo[1,5-a]quinoxalin-4-ones
  作者：Ping Chen、Joel C. Barrish、Edwin Iwanowicz、James Lin、Mark S. Bednarz、Bang-Chi Chen

  DOI：10.1016/s0040-4039(01)00697-9

  日期：2001.6

  Imidazo[1,5-alpha ]quinoxalin-4-ones were prepared in four steps starting from 1,2-phenylenediamines using a new strategy for the construction of the ring system. A key step in this new method involves the reaction of quinoxalin-2-ones with TosMIC (tosylmethyl isocyanide). (C) 2001 Elsevier Science Ltd. All rights reserved.