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 | 1251860-77-1

• 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-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
• 英文别名: 9-Hydroxy-8-[9-(9-hydroxy-3,3-dimethyl-7,10-dioxo-benzo[f]chromen-8-yl)-3,3-dimethyl-7,10-dioxo-1,2-dihydrobenzo[f]chromen-8-yl]-3,3-dimethyl-benzo[f]chromene-7,10-dione；9-hydroxy-8-[9-(9-hydroxy-3,3-dimethyl-7,10-dioxobenzo[f]chromen-8-yl)-3,3-dimethyl-7,10-dioxo-1,2-dihydrobenzo[f]chromen-8-yl]-3,3-dimethylbenzo[f]chromene-7,10-dione
• CAS: 1251860-77-1
• 化学式: C₄₅H₃₄O₁₁
• 分子量: 750.758
• InChiKey: UIVVAUBNXGNWQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  56
• 可旋转键数：
  2
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  171
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,7-二羟基萘 在 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 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

文献信息

• 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.
• Antiviral agents 3. Discovery of a novel small molecule non-nucleoside inhibitor of Hepatitis B Virus (HBV)
  作者：Ian T. Crosby、David G. Bourke、Eric D. Jones、Tyrone P. Jeynes、Susan Cox、Jonathan A.V. Coates、Alan D. Robertson

  DOI：10.1016/j.bmcl.2011.01.109

  日期：2011.3

  to remove by-products. As a result we discovered a small molecule 19 that also was a potent inhibitor of HBV. Importantly, this small molecule inhibitor of Hepatitis B Virus is also an inhibitor of Hepatitis B Virus resistant to 3TC, a bench mark of nucleoside analogues active in the treatment of Hepatitis B Virus. The development of 19 as an agent to treat HBV infections is discussed.

  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。