5-Hydroxy-15-(4-methoxyphenyl)-9,9-dimethyl-8-oxa-13,15,17-triazatetracyclo[8.7.0.02,7.013,17]heptadeca-2(7),3,5,10-tetraene-14,16-dione | 1258974-36-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-Hydroxy-15-(4-methoxyphenyl)-9,9-dimethyl-8-oxa-13,15,17-triazatetracyclo[8.7.0.02,7.013,17]heptadeca-2(7),3,5,10-tetraene-14,16-dione
• CAS: 1258974-36-5
• 化学式: C₂₂H₂₁N₃O₅
• 分子量: 407.426
• InChiKey: FKVYFWAIRQOUHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,2,4-三氮杂茂-3,5-二酮,4-(4-甲氧苯基)- 在 吡啶 、 碘苯二乙酸 、 氢氟酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.83h， 生成 5-Hydroxy-15-(4-methoxyphenyl)-9,9-dimethyl-8-oxa-13,15,17-triazatetracyclo[8.7.0.02,7.013,17]heptadeca-2(7),3,5,10-tetraene-14,16-dione
  参考文献：
  名称：

  面向多样性的合成途径构建具有不同核心骨架的多杂环苯并吡喃文库：第二部分

  摘要：

  正如我们以前的报告（的延续J.梳子。化学。2010，12（548-558），我们完成了具有特权的苯并吡喃亚结构的多杂环小分子文库的面向多样性的合成。为确保合成效率，我们利用固相平行平台和基于氟标签的溶液相平行平台，构建了一个由284个成员组成的具有6个不同核心骨架的多杂环文库，其平均纯度为87％。 5-10毫克。该库旨在最大程度地提高三维空间中离散核心骨架的骨架多样性，并使用四种不同的苯并吡喃基原料和各种结构单元来实现组合多样性。加上我们报道的苯并吡喃基文库，

  DOI：

  10.1021/co2001907

文献信息

• Discovery of Novel Benzopyranyl Tetracycles that Act as Inhibitors of Osteoclastogenesis Induced by Receptor Activator of NF-κB Ligand
  作者：Mingyan Zhu、Myung Hee Kim、Sanghee Lee、Su Jung Bae、Seong Hwan Kim、Seung Bum Park

  DOI：10.1021/jm1011269

  日期：2010.12.23

  A novel benzopyran-fused molecular framework 7ai was discovered as a specific inhibitor of RANKL-induced osteoclastogenesis using a cell-based TRAP activity assay from drug-like small-molecule libraries constructed by diversity-oriented synthesis. Its inhibitory activity was confirmed by in vitro evaluations including specific inhibition of RANKL-induced ERK phosphorylation and NF-kappa B transcriptional activation. 7ai can serve as a specific small-molecule modulator for mechanistic studies of RANKL-induced osteoclast differentiation as well as a potential lead for the development of antiresorptive drugs.
• Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents
  作者：Wansang Cho、Ja Young Koo、Yeonju Park、Keunhee Oh、Sanghee Lee、Jin-Sook Song、Myung Ae Bae、Donghyun Lim、Dong-Sup Lee、Seung Bum Park

  DOI：10.1021/acs.jmedchem.6b00954

  日期：2017.1.12

  Sepsis is one of the major causes of death worldwide when associated with multiple organ failure. However, there is a critical lack of adequate sepsis therapies because of its diverse patterns of pathogenesis. The pro-inflammatory cytokine cascade mediates sepsis pathogenesis, and high mobility group box proteins (HMGBs) play an important role as late-stage cytokines. We previously reported the small-molecule modulator, inflachromene (1d), which inhibits the release of HMGBs and, thereby, reduces the production of pro-inflammatory cytokines. In this context, we intraperitoneally administered Id to a cecal ligation and puncture (CLP)-induced mouse model of sepsis and confirmed that it successfully ameliorated sepsis pathogenesis. On the basis of a structure activity relationship study, we discovered new candidate compounds, 2j and 21, with improved therapeutic efficacy in vivo. Therefore, our study clearly demonstrates that the regulation of HMGB1 release using small molecules is a promising strategy for the treatment of sepsis.
• ANTI-INFLAMMATORY PHARMACEUTICAL COMPOSITION COMPRISING BENZOPYRANYL TETRACYCLES
  申请人：SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

  公开号：US20160038489A1

  公开（公告）日：2016-02-11

  Disclosed herein is an anti-inflammatory pharmaceutical composition comprising a benzopyranyl tetracycle compound represented by Chemical Formula 1 as an active ingredient. The compound exhibits excellent anti-inflammatory activity by perturbing the post-translational modification of the inflammation mediator HMGB, and thus finds applications in pharmaceutical compositions superior in the treatment or prevention of inflammation-related diseases.
• US9468641B2
  申请人：——

  公开号：US9468641B2

  公开（公告）日：2016-10-18
• Construction of Polyheterocyclic Benzopyran Library with Diverse Core Skeletons through Diversity-Oriented Synthesis Pathway: Part II
  作者：Mingyan Zhu、Byung Joon Lim、Minseob Koh、Seung Bum Park

  DOI：10.1021/co2001907

  日期：2012.2.13

  diversity-oriented synthesis of polyheterocyclic small-molecule library with privileged benzopyran substructure. To ensure the synthetic efficiency, we utilized the solid-phase parallel platform and the fluorous-tag-based solution-phase parallel platform to construct a 284-member polyheterocyclic library with six distinct core skeletons with an average purity of 87% on a scale of 5–10 mg. This library was designed

  正如我们以前的报告（的延续J.梳子。化学。2010，12（548-558），我们完成了具有特权的苯并吡喃亚结构的多杂环小分子文库的面向多样性的合成。为确保合成效率，我们利用固相平行平台和基于氟标签的溶液相平行平台，构建了一个由284个成员组成的具有6个不同核心骨架的多杂环文库，其平均纯度为87％。 5-10毫克。该库旨在最大程度地提高三维空间中离散核心骨架的骨架多样性，并使用四种不同的苯并吡喃基原料和各种结构单元来实现组合多样性。加上我们报道的苯并吡喃基文库，