9-hydroxy-3,3-dimethyl-3H-naphtho[2,1-b]pyran-7,10-dione | 57309-96-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 9-hydroxy-3,3-dimethyl-3H-naphtho[2,1-b]pyran-7,10-dione
• 英文别名: 9-hydroxy-3,3-dimethyl-3H-benzo[f]chromene-7,10-dione；9-Hydroxy-3,3dimethyl-3H-naphtho[2,1-b]pyran-7,10-dione
• CAS: 57309-96-3
• 化学式: C₁₅H₁₂O₄
• 分子量: 256.258
• InChiKey: POUDAKUTSBMUFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  9-hydroxy-3,3-dimethyl-3H-naphtho[2,1-b]pyran-7,10-dione 在 platinum(IV) oxide 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 9-hydroxy-8-(8'-(9''-hydroxy-3'',3''-dimethyl-7'',10''-dioxo-7'',10''-dihydro-3''H-naphtho[2,1-b]pyran-8''-yl)-3',3'-dimethyl-7',10'-dioxo-1',2',7',10'-tetrahydro-3'H-naphtho[2,1-b]pyran-9'-yl)-3,3-dimethyl-3H-naphtho[2,1-b]pyran-7,10-dione
  参考文献：
  名称：

  抗病毒剂3.乙型肝炎病毒（HBV）的新型小分子非核苷抑制剂的发现

  摘要：

  描述了乙型肝炎病毒的小分子非核苷抑制剂的发现。在我们研究香豆素衍生的萘醌“三聚体”用于治疗HIV的过程中，我们在抗病毒筛选中发现了一种有效的乙肝病毒抑制剂9。在尝试重新合成9以进行概念验证的过程中，我们更改了合成方法，以尝试减少副反应并难以除去副产物。结果，我们发现了一个小分子19，它也是HBV的有效抑制剂。重要的是，这种乙型肝炎病毒的小分子抑制剂也是抗3TC的乙型肝炎病毒的抑制剂，3TC是在治疗乙型肝炎病毒中具有活性的核苷类似物的基准。发展历程19 作为治疗乙肝病毒感染的药物进行了讨论。

  DOI：

  10.1016/j.bmcl.2011.01.109
• 作为产物：
  描述：

  3,3-dimethyl-3H-naphtho[2,1-b]pyran-9,10-dione 在 sodium dithionite 、 potassium tert-butylate 、 氧气 作用下， 以 水 、 甲苯 、 叔丁醇 为溶剂， 反应 0.17h， 以61%的产率得到9-hydroxy-3,3-dimethyl-3H-naphtho[2,1-b]pyran-7,10-dione
  参考文献：
  名称：

  Antiviral Agents. I. Synthesis and Antiviral Evaluation of Trimeric Naphthoquinone Analogues of Conocurvone

  摘要：

  Conocurvone 是一种从澳大利亚特有灌木 Conosperum sp.（原生植物科）中分离出来的新型天然产物，具有抗艾滋病毒的活性，但它是一种高亲脂性化合物，这表明它的水溶性和生物利用度可能存在问题。本文介绍了一种利用 2-羟基萘醌和 2,3-二卤醌缩合合成三聚萘醌的通用简便方法。报告还介绍了应用这种方法合成一系列更简单、亲油性更低的三聚萘醌简单类似物 conocurvone 及其抗 HIV 活性。

  DOI：

  10.1071/ch08177

文献信息

• [EN] ANTIVIRAL AGENTS<br/>[FR] AGENTS ANTIVIRAUX
  申请人：UNIV MONASH

  公开号：WO2005095376A1

  公开（公告）日：2005-10-13

  The present invention provides a method of treatment or prophylaxis of hepatitis B virus in a subject comprising administering an effective amount of a compound of formula (1) or a pharmaceutically acceptable derivative, salt or prodrug thereof. In addition, there is provided compounds of formula (1) and pharmaceutical compositions thereof. Further, methods of preparing compounds of formula (1) are disclosed.

  本发明提供了一种治疗或预防乙型肝炎病毒的方法，包括向受试者施用化合物式（1）或其药学上可接受的衍生物、盐或前药的有效量。此外，还提供了化合物式（1）及其药物组成物。此外，还公开了制备化合物式（1）的方法。
• Antiviral agents
  申请人：Coates Jonathan Alan Victor

  公开号：US20090170926A1

  公开（公告）日：2009-07-02

  The present invention provides a method of treatment or prophylaxis of hepatitis B virus in a subject comprising administering an effective amount of a compound of formula ( 1 ) or a pharmaceutically acceptable derivative, salt or prodrug thereof. In addition, there is provided compounds of formula ( 1 ) and pharmaceutical compositions thereof. Further, methods of preparing compounds of formula ( 1 ) are disclosed.

  本发明提供了一种治疗或预防乙型肝炎病毒的方法，包括向受试者施用化合物（1）的有效量或其药学上可接受的衍生物、盐或前药。此外，还提供了化合物（1）及其药物组合物。此外，还公开了制备化合物（1）的方法。
• A New Method for the Synthesis of 2-Hydroxy-3-nitro-1,4-naphthoquinones:  Application to Regiospecific Preparation of Unsymmetrical Nitrobiquinones
  作者：Min Yu、Helena C. Malinakova、Kenneth W. Stagliano

  DOI：10.1021/jo060825c

  日期：2006.8.1

  Novel 2-hydroxy-3-nitro-1,4-naphthoquinones were synthesized by an improved method utilizing nitronium tetrafluoroborate in high yields. A subsequent conversion to 2-chloro-3-nitro-1,4-naphthoquinones and a substitution of the chlorine by hydroxyquinone anions yielded 3-nitro-2,2‘-binaphthoquinones with a complete regiocontrol.

  利用改进的方法，利用四氟硼酸硝基鎓高产率地合成了新型的2-羟基-3-硝基-1,4-萘醌。随后转化为2-氯-3-硝基-1,4-萘醌并用羟基醌阴离子取代氯，得到具有完全区域控制的3-硝基-2,2'-联萘醌。
• Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone
  作者：Kenneth W. Stagliano、Ashkan Emadi、Zhenhai Lu、Helena C. Malinakova、Barry Twenter、Min Yu、Louis E. Holland、Amanda M. Rom、John S. Harwood、Ronak Amin、Allison A. Johnson、Yves Pommier

  DOI：10.1016/j.bmc.2006.04.034

  日期：2006.8

  Unsymmetrical biquinone and trimeric quinone derivatives were synthesized using halotriflate-biselectrophilic naphthoquinones through stepwise regioselective quinone substitution chemistry and evaluated for their ability to inhibit the cytopathogenic effects of HIV-1 using an MTT colorimetric assay. Compounds were also screened for their ability to inhibit the activity of HIV-1 integrase in vitro. Pyranylated trimeric quinones and biquinones exhibited both antiviral activity and integrase inhibitory activity. Conocurvone 1 and trimeric quinone 21 were the most potent HIV integrase inhibitors in the series. All of the biquinones showed HIV inhibitory activity. Simple methoxy substituted biquinones did not inhibit HIV-1 integrase. Published by Elsevier Ltd.
• Antiviral agents 2. Synthesis of trimeric naphthoquinone analogues of conocurvone and their antiviral evaluation against HIV
  作者：Ian T. Crosby、David G. Bourke、Eric D. Jones、Paula J. de Bruyn、David Rhodes、Nick Vandegraaff、Susan Cox、Jonathan A.V. Coates、Alan D. Robertson

  DOI：10.1016/j.bmc.2010.06.105

  日期：2010.9

  The synthesis of a new series of conocurvone analogues is presented that explores the importance of the pyran rings of conocurvone, their degree of unsaturation as well as the role of alkoxy functionalities as pyran ring replacements, for the inhibition of the HIV-1 integrase (IN) enzyme. Difficulties in synthesising a trimeric naphthoquinone where the central quinone bears a peri-dihydropyran ring was attributed to distortion of the electrophilic dihaloquinone successfully utilised in the past. Increased electron density could also be a factor in reducing reactivity. The desired central dihydropyran bearing trimeric naphthoquinone was successfully synthesised by using a more reactive bromo-tosyloxyquinone intermediate. A maleimide derivative, where the central quinone between the pendant hydroxyquinones was replaced, was successfully synthesised and although it exhibited comparable enzyme inhibitory activity it had negligible HIV inhibitory cellular activity. Compounds were assessed for activity in both in vitro assays using purified recombinant HIV-1 IN and demonstrated superior or comparable activity to conocurvone derivatives previously reported. (C) 2010 Elsevier Ltd. All rights reserved.