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coscinafuran

中文名称
——
中文别名
——
英文名称
coscinafuran
英文别名
(5aR,5bS,7aS,11aS,11bR,13aS)-5b,8,8,11a-tetramethyl-4,5,5a,6,7,7a,9,10,11,11b,12,13-dodecahydrophenanthro[1,2-g][1]benzofuran-13a-carbaldehyde
coscinafuran化学式
CAS
——
化学式
C25H36O2
mdl
——
分子量
368.56
InChiKey
BJZJGWCRTFNBRU-BWNQIZJUSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    7
  • 重原子数:
    27
  • 可旋转键数:
    1
  • 环数:
    5.0
  • sp3杂化的碳原子比例:
    0.8
  • 拓扑面积:
    30.2
  • 氢给体数:
    0
  • 氢受体数:
    2

反应信息

  • 作为反应物:
    描述:
    coscinafuran 在 sodium tetrahydroborate 作用下, 以 甲醇 为溶剂, 以70%的产率得到[(5aR,5bS,7aS,11aS,11bR,13aR)-5b,8,8,11a-tetramethyl-4,5,5a,6,7,7a,9,10,11,11b,12,13-dodecahydrophenanthro[1,2-g][1]benzofuran-13a-yl]methanol
    参考文献:
    名称:
    Binding Mechanism of the Farnesoid X Receptor Marine Antagonist Suvanine Reveals a Strategy To Forestall Drug Modulation on Nuclear Receptors. Design, Synthesis, and Biological Evaluation of Novel Ligands
    摘要:
    Here, we report suvanine, a marine sponge sesterterpene, as an antagonist of the mammalian bile acid sensor farnesoid-X-receptor (FXR). Using suvanine as a template, we shed light on the molecular bases of FXR antagonism, identifying the essential conformational changes responsible for the transition from the agonist to the antagonist form. Molecular characterization of the nuclear corepressor NCoR and coactivator Src-1 revealed that receptor conformational changes are associated with a specific dynamic of recruitment of these cofactors to the promoter of OST alpha, a FXR regulated gene. Using suvanine as a novel hit, a library of semisynthetic derivatives has been designed and prepared, leading to pharmacological profiles ranging from agonism to antagonism toward FXR. Deep pharmacological evaluation demonstrated that derivative 19 represents a new chemotype of FXR modulator, whereas alcohol 6, with a simplified molecular scaffold, exhibits excellent antagonistic activity.
    DOI:
    10.1021/jm400419e
  • 作为产物:
    描述:
    suvanine吡啶 作用下, 以 1,4-二氧六环 为溶剂, 反应 3.0h, 以70%的产率得到(1S,2R,4aS,4bS,8aS,10aR)-1-[2-(furan-3-yl)ethyl]-4b,8,8,10a-tetramethyl-2,3,4,4a,5,6,7,8a,9,10-decahydro-1H-phenanthrene-2-carbaldehyde
    参考文献:
    名称:
    Binding Mechanism of the Farnesoid X Receptor Marine Antagonist Suvanine Reveals a Strategy To Forestall Drug Modulation on Nuclear Receptors. Design, Synthesis, and Biological Evaluation of Novel Ligands
    摘要:
    Here, we report suvanine, a marine sponge sesterterpene, as an antagonist of the mammalian bile acid sensor farnesoid-X-receptor (FXR). Using suvanine as a template, we shed light on the molecular bases of FXR antagonism, identifying the essential conformational changes responsible for the transition from the agonist to the antagonist form. Molecular characterization of the nuclear corepressor NCoR and coactivator Src-1 revealed that receptor conformational changes are associated with a specific dynamic of recruitment of these cofactors to the promoter of OST alpha, a FXR regulated gene. Using suvanine as a novel hit, a library of semisynthetic derivatives has been designed and prepared, leading to pharmacological profiles ranging from agonism to antagonism toward FXR. Deep pharmacological evaluation demonstrated that derivative 19 represents a new chemotype of FXR modulator, whereas alcohol 6, with a simplified molecular scaffold, exhibits excellent antagonistic activity.
    DOI:
    10.1021/jm400419e
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文献信息

  • Binding Mechanism of the Farnesoid X Receptor Marine Antagonist Suvanine Reveals a Strategy To Forestall Drug Modulation on Nuclear Receptors. Design, Synthesis, and Biological Evaluation of Novel Ligands
    作者:Francesco Saverio Di Leva、Carmen Festa、Claudio D’Amore、Simona De Marino、Barbara Renga、Maria Valeria D’Auria、Ettore Novellino、Vittorio Limongelli、Angela Zampella、Stefano Fiorucci
    DOI:10.1021/jm400419e
    日期:2013.6.13
    Here, we report suvanine, a marine sponge sesterterpene, as an antagonist of the mammalian bile acid sensor farnesoid-X-receptor (FXR). Using suvanine as a template, we shed light on the molecular bases of FXR antagonism, identifying the essential conformational changes responsible for the transition from the agonist to the antagonist form. Molecular characterization of the nuclear corepressor NCoR and coactivator Src-1 revealed that receptor conformational changes are associated with a specific dynamic of recruitment of these cofactors to the promoter of OST alpha, a FXR regulated gene. Using suvanine as a novel hit, a library of semisynthetic derivatives has been designed and prepared, leading to pharmacological profiles ranging from agonism to antagonism toward FXR. Deep pharmacological evaluation demonstrated that derivative 19 represents a new chemotype of FXR modulator, whereas alcohol 6, with a simplified molecular scaffold, exhibits excellent antagonistic activity.
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