6,7-methylenedioxy-4-quinolone | 35478-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6,7-methylenedioxy-4-quinolone
• 英文别名: 5H-[1,3]dioxolo[4,5-g]quinolin-8-one
• CAS: 35478-79-6
• 化学式: C₁₀H₇NO₃
• 分子量: 189.17
• InChiKey: GJEILVUIMNTTNZ-UHFFFAOYSA-N

物化性质

• 熔点：
  276 °C
• 沸点：
  394.0±37.0 °C(Predicted)
• 密度：
  1.496±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-methylenedioxy-4-quinolone 在 钯 palladium diacetate 、 甲酸 、 溶剂黄146 、 三乙胺 、 三(邻甲基苯基)磷 、 silver carbonate 、 三氯氧磷 、 苯酚 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.5h， 生成 GENZ-644282抑制剂
  参考文献：
  名称：

  5-(2-Aminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones:  Variation of N-Alkyl Substituents Modulates Sensitivity to Efflux Transporters Associated with Multidrug Resistance

  摘要：

  5H-8,9-Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo [c, h]-[1,6]naphthyridin-6-one (ARC-111) has potent TOP1-targeting activity and pronounced antitumor activity. Several analogues of ARC-111 were synthesized with NH2, N-alkyl, N,N-dialkyl, pyrrolidinyl, piperidinyl, and piperazinyl substituents at the 2-position of the 5-ethyl group. The relative TOP1-targeting activity and cytotoxicity of these structural analogues were assessed in RPMI8402 and P388 tumor cells and their camptothecin-resistant variants CPT-K5 and P388/CPT45, respectively. Potent TOP1-targeting activity was retained within a series of mono N-alkyl analogues that included NHCH2CH3, NHCH(CH3)(2), and NHC(CH3)(3). TOP1-targeting activity was diminished by the presence of a N-benzyl moiety. In a comparison of a series of N-alkyl-N-isopropyl analogues, activity decreased in the order CH3 > CH2CH3 > CH(CH3)(2). Cytotoxicity in RPMI8402 and P388 did correlate with TOP1-targeting activity. Cytotoxic activity was also determined in KB3-1 cells and its variants KB/V-1 and KBH5.0. As KB/V-1 cells overexpress MDR1 and KBH5.0 cells overexpress BCRP, decreased cytotoxicity in these cell lines relative to the parent cell line is indicative of compounds that are substrates for these efflux transporters. In view of their diminished cytotoxicity in KB/V-1 cells, it appears that the likely demethylated metabolites of ARC-111, i.e., where NH2 or NHCH3 replaces the N(CH3)(2) at the 2-position of the 5-ethyl substituent, are substrates for MDR1. In contrast, no significant difference in cytotoxicity among these three cell lines was observed with other N-alkyl analogues, including NHC2H5, NHCH(CH3)(2), NHC(CH3)(3), N(CH3)(2), N(CH2CH3)(2), NCH3(CH(CH)(3))(2)), and either the pyrrolidinyl or the piperidinyl analogues. The 2-(piperazinyl) analogues were associated with diminished cytotoxicity in KB/V-1 cells, suggesting that the second basic amino substituent is associated with their recognition as substrates by MDR1. Comparative studies on the antitumor activity of ARC-111 and its N-demethylated derivatives (the NHCH3 and NH2 analogues) against SJ-BT45 medulloblastoma xenografts in scid mice revealed that the secondary amine metabolite is at least as active as ARC-111 in vivo, although the primary amine derivative was significantly less potent.

  DOI：

  10.1021/jm049447z
• 作为产物：
  描述：

  8-羟基[1,3]二氧代lo[4,5-g]喹啉-7-羧酸乙酯 在 二苯醚 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 21.5h， 生成 6,7-methylenedioxy-4-quinolone
  参考文献：
  名称：

  [EN] METHODS FOR TREATING GASTRIC AND PANCREATIC MALIGNANCIES
  [FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS GASTRIQUES ET PANCRÉATIQUES

  摘要：

  该发明提供了治疗胰腺癌或胃癌或其转移的方法和药物组合物。

  公开号：

  WO2012015901A1
• 作为试剂：
  描述：

  5,8-二氢-8-氧代-2H-1,3-二氧杂环戊并(4,5-g)喹啉-7-羧酸 、 喹啉 在 乙醇 、 乙醚 、 6,7-methylenedioxy-4-quinolone 、 ( 2x ) 、 水 作用下， 以 乙醚 为溶剂， 反应 16.0h， 以yielded analytically pure 6,7-methylenedioxy-4-quinolinol as a pale yellow solid, m.p. 288°-289°的产率得到6,7-methylenedioxy-4-quinolone
  参考文献：
  名称：

  Process for piperidine intermediates for quinine, quinidine and analogs

  摘要：

  奎宁、奎尼丁及其类似物是通过将4-喹诺林锂化合物与4,5-内消旋-5-乙基（或乙烯基）喹曲啶-2.ε.-羧醛或相应的喹曲啶-2-羧酸烷基酯反应制备的。此外，还描述了4,5-内消旋-5-乙基（或乙烯基）喹曲啶-2.ε.-羧醛和4,5-外消旋-5-乙基（或乙烯基）喹曲啶-2.ε.-羧酸及其酯类的制备方法。最终产品可用作抗疟疾和抗心律失常药物。

  公开号：

  US03931192A1

文献信息

• Novel and convenient synthesis of 4(1H)quinolones
  作者：Jan Tois、Mikko Vahermo、Ari Koskinen

  DOI：10.1016/j.tetlet.2004.12.046

  日期：2005.1

  A rapid two-step synthesis of 4(1H)quinolones is described. The first step involves condensation of o-nitroacetophenone with N,N-dimethylformamide dimethylacetal yielding highly crystalline enamines. In the second step a reductive cyclization is achieved under catalytic transfer hydrogenation (CTH) conditions. In all cases, the total time of this process was less than 3 h.

  描述了一种快速的两步合成4（1 H）喹诺酮的方法。第一步涉及邻硝基苯乙酮与N，N-二甲基甲酰胺二甲基乙缩醛的缩合，生成高度结晶的烯胺。在第二步中，在催化转移氢化（CTH）条件下实现还原环化。在所有情况下，该过程的总时间少于3小时。
• Direct C-3-Alkenylation of Quinolones via Palladium-Catalyzed CH Functionalization
  作者：Mingzong Li、Liangxi Li、Haibo Ge

  DOI：10.1002/adsc.201000364

  日期：2010.10.4

  An unprecedented C-3-alkenylation of quinolones was reported through palladium-catalyzed CH functionalization with 1% catalyst loading. This method provides an efficient route to a variety of new quinolone derivatives.

  据报道，钯负载量为1％时，钯催化的CH官能化使喹诺酮类化合物的C-3-烯基化程度达到前所未有的水平。该方法为生产各种新的喹诺酮衍生物提供了有效的途径。
• Highly Enantioselective Catalytic Addition of Grignard Reagents to N‐Heterocyclic Acceptors
  作者：Yafei Guo、Syuzanna R. Harutyunyan

  DOI：10.1002/anie.201906237

  日期：2019.9.9

  greatly sought after because of their significance in medicinal chemistry. Described here is the first general catalytic methodology to access a wide variety of chiral 2‐ and 4‐substituted tetrahydro‐quinolones, dihydro‐4‐pyridones, and piperidones with excellent yields and enantioselectivities, utilizing a single catalyst system.

  由于手性N-杂环分子支架在药物化学中的重要性，因此备受追捧。这里描述的是第一种通用催化方法，它利用单一催化剂系统，以优异的收率和对映选择性获得了各种手性2和4取代的四氢喹诺酮，二氢4吡啶酮和哌啶酮。
• Synthesis and biological evaluation of new heterocyclic quinolinones as anti-parasite and anti-HIV drug candidates
  作者：Albert Darque、Aurélien Dumètre、Sébastien Hutter、Gilles Casano、Maxime Robin、Christophe Pannecouque、Nadine Azas

  DOI：10.1016/j.bmcl.2009.08.013

  日期：2009.10

  We have synthesized quinolinones with potential antiparasitic and anti-HIV activities by an original two-step method involving microwave irradiation and have evaluated their activities against Plasmodium falciparum, Leishmania donovani, Trichomonas vaginalis, and HIV. None of the tested compounds had been previously described using this method of synthesis. One of the compounds had interesting antiparasitic

  我们已经通过涉及微波辐射的原始两步法合成了具有潜在抗寄生虫和抗HIV活性的喹啉酮，并评估了它们对恶性疟原虫，杜氏利什曼原虫，阴道毛滴虫和HIV的活性。以前没有使用这种合成方法描述过测试化合物。其中一种化合物具有令人感兴趣的抗寄生虫和抗HIV活性，可以通过用不同的基团取代来提高其活性。
• [EN] METHODS FOR TREATING HEMATOLOGICAL MALIGNANCIES<br/>[FR] MÉTHODES DE TRAITEMENT DE MALIGNITÉS HÉMATOLOGIQUES
  申请人：GENZYME CORP

  公开号：WO2012015875A1

  公开（公告）日：2012-02-02

  The invention provides methods and pharmaceutical compositions for treating certain hematological cancers.

  这项发明提供了治疗特定血液系统癌症的方法和药物组合物。