| 1403482-38-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1403482-38-1
• 化学式: C₂₂H₃₃NO₈
• 分子量: 439.506
• InChiKey: CXAWYKSJLAZMJN-YKXHTNLXSA-N

物化性质

• 沸点：
  553.4±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.57
• 重原子数：
  31.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  93.71
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  在 吡啶 、 盐酸 、 sodium tetrahydroborate 、 正丁基锂 、 水 、 碘 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 一水合肼 、 三乙胺 、 sodium iodide 、 lithium hexamethyldisilazane 、 sodium sulfite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 112.36h， 生成
  参考文献：
  名称：

  Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2

  摘要：

  Epigenetic regulation is involved in numerous physiological and pathogenic processes. Among the key regulators that orchestrate epigenetic signaling are over 50 human protein lysine methyltransferases (PKMTs). Interrogation of the functions of individual PKMTs can be facilitated by target-specific PKMT inhibitors. Given the emerging need for such small molecules, we envisioned an approach to identify target-specific methyltransferase inhibitors by screening privileged small-molecule scaffolds against diverse methyltransferases. In this work, we demonstrated the feasibility of such an approach by identifying the inhibitors of SETD2. N-propyl sinefungin (Pr-SNF) was shown to interact preferentially with SETD2 by matching the distinct transition-state features of SETD2's catalytically active conformer. With Pr-SNF as a structure probe, we further revealed the dual roles of SETD2's post-SET loop in regulating substrate access through a distinct topological reconfiguration. Privileged sinefungin scaffolds are expected to have broad use as structure and chemical probes of methyltransferases.

  DOI：

  10.1021/ja307060p
• 作为产物：
  描述：

  Benzyl ((S)-1-((3aR,4R,6R,6aR)-6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)pent-4-en-2-yl)carbamate 在 二甲基硫 、 臭氧 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以77%的产率得到
  参考文献：
  名称：

  Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2

  摘要：

  Epigenetic regulation is involved in numerous physiological and pathogenic processes. Among the key regulators that orchestrate epigenetic signaling are over 50 human protein lysine methyltransferases (PKMTs). Interrogation of the functions of individual PKMTs can be facilitated by target-specific PKMT inhibitors. Given the emerging need for such small molecules, we envisioned an approach to identify target-specific methyltransferase inhibitors by screening privileged small-molecule scaffolds against diverse methyltransferases. In this work, we demonstrated the feasibility of such an approach by identifying the inhibitors of SETD2. N-propyl sinefungin (Pr-SNF) was shown to interact preferentially with SETD2 by matching the distinct transition-state features of SETD2's catalytically active conformer. With Pr-SNF as a structure probe, we further revealed the dual roles of SETD2's post-SET loop in regulating substrate access through a distinct topological reconfiguration. Privileged sinefungin scaffolds are expected to have broad use as structure and chemical probes of methyltransferases.

  DOI：

  10.1021/ja307060p

文献信息

• [EN] METHYLTRANSFERASE INHIBITORS FOR TREATING CANCER<br/>[FR] INHIBITEURS DE MÉTHYLTRANSFÉRASE POUR TRAITER LE CANCER
  申请人：SLOAN KETTERING INST CANCER

  公开号：WO2013063417A1

  公开（公告）日：2013-05-02

  Compounds having methyltransferase inhibitory activity are disclosed. The compounds are amino acids, esters and amides having a common core based on adenosine or deazaadenosine and are useful in the treatment of cancer and similar diseases associated with inappropriate methyltransferase activity.

  揭示了具有甲基转移酶抑制活性的化合物。这些化合物是氨基酸、酯和酰胺，具有基于腺苷或去氮腺苷的共同核心，并且在治疗与不适当的甲基转移酶活性相关的癌症和类似疾病中非常有用。