inflachromene | 908568-01-4

• 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: inflachromene
• 英文别名: 5-hydroxy-9,9-dimethyl-15-phenyl-8-oxa-13,15,17-triazatetracyclo[8.7.0.02,7.013,17]heptadeca-2(7),3,5,10-tetraene-14,16-dione
• CAS: 908568-01-4
• 化学式: C₂₁H₁₉N₃O₄
• 分子量: 377.4
• InChiKey: VVOXDJYPDCSQMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  inflachromene 在 palladium on carbon 、 氢气 作用下， 以100%的产率得到5-Hydroxy-9,9-dimethyl-15-phenyl-8-oxa-13,15,17-triazatetracyclo[8.7.0.02,7.013,17]heptadeca-2(7),3,5-triene-14,16-dione
  参考文献：
  名称：

  Discovery of Novel Benzopyranyl Tetracycles that Act as Inhibitors of Osteoclastogenesis Induced by Receptor Activator of NF-κB Ligand

  摘要：

  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.

  DOI：

  10.1021/jm1011269
• 作为产物：
  描述：

  ((2,2-dimethyl-3-vinyl-2H-chromen-7-yl)oxy)(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)diisopropylsilane 在 吡啶 、 氢氟酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.5h， 生成 inflachromene
  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

• Concise and diversity-oriented synthesis of novel scaffolds embedded with privileged benzopyran motif
  作者：Sung Kon Ko、Hwan Jong Jang、Eunha Kim、Seung Bum Park

  DOI：10.1039/b606341a

  日期：——

  A branching DOS strategy for an unbiased natural product-like library with embedded privileged benzopyran motif was established to provide complexity and diversity of resulting heterocycles with desired drug-likeness. The importance of skeletal diversity conducted on a privileged substructure was demonstrated through the biological evaluation of a small molecule library representing 22 unique core skeletons via in vitro cytotoxicity assay.

  建立了一种分枝的DOS策略，用于制备无偏倚的、类似天然产物库的分子库，其中嵌入特权苯并吡喃结构基元，以提供具有期望的类药性的杂环化合物的复杂性和多样性。通过体外细胞毒性检测，对代表22种独特核心骨架的小分子库进行生物活性评估，展示了以特权子结构为基础的骨架多样性的重要性。
• 신규한 벤조피라닐 테트라사이클 화합물, 및 이를 포함하는 우수한 항염증 효과를 갖는 약학적 조성물
  申请人：Spark Biopharma, Inc (주)스파크바이오파마(120160160632) Corp. No ▼ 110111-5956482BRN ▼441-88-00285

  公开号：KR20190044366A

  公开（公告）日：2019-04-30

  본 발명은 신규한 하기 화학식3(2j) 또는 5(2l)의 화합물, 및 이를 포함하는 우수한 항염증 효과를 갖는 약학적 조성물에 관한 것이다. 상기 화합물들은 염증 유발 인자인 HMGB1 단백질이 핵에서 세포질로 이동되는 것을 저해함으로써 우수한 염증 억제 효과를 가지며, 특히 패혈증 등에 대한 우수한 치료 효과 또는 예방 효과를 갖는다. [화학식 3] [화학식 5]

  本发明涉及一种新的化合物，化学式为3(2j)或5(2l)，以及包含该化合物的具有优异抗炎作用的药学组合物。这些化合物通过阻止炎症诱导因子HMGB1蛋白从细胞核移动到细胞质，具有优异的抗炎效果，特别是对败血症等具有优异治疗效果或预防效果。【化学式3】【化学式5】
• 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